Protein Kinases and Caspases: Bidirectional Interactions in Apoptosis
Stephanie A. Zukowski
University of Western Ontario, Department of Biochemistry, Schulich School of Medicine & Dentistry, N6A 5C1, London, ON Canada
Search for more papers by this authorDavid W. Litchfield
University of Western Ontario, Department of Biochemistry, Schulich School of Medicine & Dentistry, N6A 5C1, London, ON Canada
Search for more papers by this authorStephanie A. Zukowski
University of Western Ontario, Department of Biochemistry, Schulich School of Medicine & Dentistry, N6A 5C1, London, ON Canada
Search for more papers by this authorDavid W. Litchfield
University of Western Ontario, Department of Biochemistry, Schulich School of Medicine & Dentistry, N6A 5C1, London, ON Canada
Search for more papers by this authorHeinz-Bernhard Kraatz
University of Toronto, Phys. & Environmental Sciences, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada
Search for more papers by this authorSanela Martic
Oakland University, Dept. of Chemistry, 2200 North Squirrel Road, Rochester, MI 48309, United States
Search for more papers by this authorSummary
This chapter highlights the prevalence of protein kinase signaling in apoptotic pathways and emphasizes the emergence of global strategies to systematically investigate bidirectional crosstalk between protein kinase phosphorylation and caspase-mediated proteolysis in the propagation of irreversible apoptotic induction. Caspases are classified as cysteine proteases that catalyze irreversible cleavage of peptide bonds C-terminal to aspartic acid residues. The apoptotic role of protein kinases is of interest because posttranslational phosphorylation of both caspases and caspase substrates affects caspase functionality, and conversely, a variety of protein kinases are proteolytically digested by caspases to facilitate or prevent apoptosis. Throughout this chapter, examples have been provided highlighting the complex interactions between protein kinases and caspases that facilitate the progression of apoptosis. The emergence of novel strategies involving proteomics, computational approaches, and techniques designed to monitor the spatial and temporal induction of apoptotic pathways within intact cells offers comprehensive new insights regarding kinase-caspase interactions.
References
- Manning, G., Whyte, D.B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science, 298, 1912–1934.
- Hunter, T. (2000) Signaling--2000 and beyond. Cell, 100, 113–127.
- Franklin, R.A. and McCubrey, J.A. (2000) Kinases: positive and negative regulators of apoptosis. Leukemia, 14, 2019–2034.
- Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell, 100, 57–70.
- Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646–674.
- Kurokawa, M. and Kornbluth, S. (2009) Caspases and kinases in a death grip. Cell, 138, 838–854.
- Parrish, A.B., Freel, C.D., and Kornbluth, S. (2013) Cellular mechanisms controlling caspase activation and function. Cold Spring Harb. Perspect. Biol., 5. doi: 10.1101/cshperspect.a008672
- Dix, M.M., Simon, G.M., Wang, C., Okerberg, E., Patricelli, M.P., and Cravatt, B.F. (2012) Functional interplay between caspase cleavage and phosphorylation sculpts the apoptotic proteome. Cell, 150, 426–440.
- Duncan, J.S., Turowec, J.P., Duncan, K.E., Vilk, G., Wu, C., Luscher, B., Li, S.S., Gloor, G.B., and Litchfield, D.W. (2011) A peptide-based target screen implicates the protein kinase CK2 in the global regulation of caspase signaling. Sci. Signal., 4, ra30.
- Turowec, J.P., Zukowski, S.A., Knight, J.D., Smalley, D.M., Graves, L.M., Johnson, G.L., Li, S.S., Lajoie, G.A., and Litchfield, D.W. (2014) An unbiased proteomic screen reveals caspase cleavage is positively and negatively regulated by substrate phosphorylation. Mol. Cell. Proteomics, 13, 1184–1197.
- Hopkins, A.L. and Groom, C.R. (2002) The druggable genome. Nat. Rev. Drug Discov., 1, 727–730.
- Cohen, P. (2002) Protein kinases--the major drug targets of the twenty-first century? Nat. Rev. Drug Discov., 1, 309–315.
- Volkamer, A., Eid, S., Turk, S., Jaeger, S., Rippmann, F., and Fulle, S. (2015) Pocketome of human kinases: prioritizing the ATP binding sites of (yet) untapped protein kinases for drug discovery. J. Chem. Inf. Model.
- Burgoyne, L.A. (1999) The mechanisms of pyknosis: hypercondensation and death. Exp. Cell Res., 248, 214–222.
- Kerr, J.F., Wyllie, A.H., and Currie, A.R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 26, 239–257.
- Nagata, S. (2000) Apoptotic DNA fragmentation. Exp. Cell Res., 256, 12–18.
- Liu, X., Zou, H., Slaughter, C., and Wang, X. (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell, 89, 175–184.
- Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., and Nagata, S. (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 391, 43–50.
- Sakahira, H., Enari, M., and Nagata, S. (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature, 391, 96–99.
- Galluzzi, L., Vitale, I., Abrams, J.M., Alnemri, E.S., Baehrecke, E.H., Blagosklonny, M.V., Dawson, T.M., Dawson, V.L., El-Deiry, W.S., Fulda, S., Gottlieb, E., Green, D.R., Hengartner, M.O., Kepp, O., Knight, R.A., Kumar, S., Lipton, S.A., Lu, X., Madeo, F., Malorni, W., Mehlen, P., Nunez, G., Peter, M.E., Piacentini, M., Rubinsztein, D.C., Shi, Y., Simon, H.U., Vandenabeele, P., White, E., Yuan, J., Zhivotovsky, B., Melino, G., and Kroemer, G. (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ., 19, 107–120.
- Pop, C. and Salvesen, G.S. (2009) Human caspases: activation, specificity, and regulation. J. Biol. Chem., 284, 21777–21781.
- Timmer, J.C., Zhu, W., Pop, C., Regan, T., Snipas, S.J., Eroshkin, A.M., Riedl, S.J., and Salvesen, G.S. (2009) Structural and kinetic determinants of protease substrates. Nat. Struct. Mol. Biol., 16, 1101–1108.
- Timmer, J.C. and Salvesen, G.S. (2007) Caspase substrates. Cell Death Differ., 14, 66–72.
- McStay, G.P., Salvesen, G.S., and Green, D.R. (2008) Overlapping cleavage motif selectivity of caspases: implications for analysis of apoptotic pathways. Cell Death Differ., 15, 322–331.
- Tozser, J., Bagossi, P., Zahuczky, G., Specht, S.I., Majerova, E., and Copeland, T.D. (2003) Effect of caspase cleavage-site phosphorylation on proteolysis. Biochem. J., 372, 137–143.
- Wajant, H. (2002) The fas signaling pathway: more than a paradigm. Science, 296, 1635–1636.
- Schutze, S., Tchikov, V., and Schneider-Brachert, W. (2008) Regulation of TNFR1 and CD95 signalling by receptor compartmentalization. Nat. Rev. Mol. Cell Biol., 9, 655–662.
- Mehlen, P. and Bredesen, D.E. (2011) Dependence receptors: from basic research to drug development. Sci. Signal., 4, mr2.
- Bredesen, D.E., Mehlen, P., and Rabizadeh, S. (2005) Receptors that mediate cellular dependence. Cell Death Differ., 12, 1031–1043.
- Guenebeaud, C., Goldschneider, D., Castets, M., Guix, C., Chazot, G., Delloye-Bourgeois, C., Eisenberg-Lerner, A., Shohat, G., Zhang, M., Laudet, V., Kimchi, A., Bernet, A., and Mehlen, P. (2010) The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Mol. Cell, 40, 863–876.
- Mille, F., Thibert, C., Fombonne, J., Rama, N., Guix, C., Hayashi, H., Corset, V., Reed, J.C., and Mehlen, P. (2009) The patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. Nat. Cell Biol., 11, 739–746.
- Forcet, C., Ye, X., Granger, L., Corset, V., Shin, H., Bredesen, D.E., and Mehlen, P. (2001) The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation. Proc. Natl. Acad. Sci. U.S.A., 98, 3416–3421.
- Lavrik, I., Golks, A., and Krammer, P.H. (2005) Death receptor signaling. J. Cell Sci., 118, 265–267.
- Ashkenazi, A. and Dixit, V.M. (1999) Apoptosis control by death and decoy receptors. Curr. Opin. Cell Biol., 11, 255–260.
- Ashkenazi, A. and Dixit, V.M. (1998) Death receptors: signaling and modulation. Science, 281, 1305–1308.
- French, L.E. and Tschopp, J. (2003) Protein-based therapeutic approaches targeting death receptors. Cell Death Differ., 10, 117–123.
- Kischkel, F.C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P.H., and Peter, M.E. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J., 14, 5579–5588.
- Muzio, M., Chinnaiyan, A.M., Kischkel, F.C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J.D., Zhang, M., Gentz, R., Mann, M., Krammer, P.H., Peter, M.E., and Dixit, V.M. (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell, 85, 817–827.
- Chinnaiyan, A.M., Tepper, C.G., Seldin, M.F., O'Rourke, K., Kischkel, F.C., Hellbardt, S., Krammer, P.H., Peter, M.E., and Dixit, V.M. (1996) FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J. Biol. Chem., 271, 4961–4965.
- Deveraux, Q.L., Roy, N., Stennicke, H.R., Van Arsdale, T., Zhou, Q., Srinivasula, S.M., Alnemri, E.S., Salvesen, G.S., and Reed, J.C. (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J., 17, 2215–2223.
- Bertrand, M.J., Milutinovic, S., Dickson, K.M., Ho, W.C., Boudreault, A., Durkin, J., Gillard, J.W., Jaquith, J.B., Morris, S.J., and Barker, P.A. (2008) cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell, 30, 689–700.
- Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J.L., Schroter, M., Burns, K., Mattmann, C., Rimoldi, D., French, L.E., and Tschopp, J. (1997) Inhibition of death receptor signals by cellular FLIP. Nature, 388, 190–195.
- Martin, D.A., Siegel, R.M., Zheng, L., and Lenardo, M.J. (1998) Membrane oligomerization and cleavage activates the caspase-8 (FLICE/MACHalpha1) death signal. J. Biol. Chem., 273, 4345–4349.
- Salvesen, G.S. and Dixit, V.M. (1999) Caspase activation: the induced-proximity model. Proc. Natl. Acad. Sci. U.S.A., 96, 10964–10967.
- Muzio, M., Stockwell, B.R., Stennicke, H.R., Salvesen, G.S., and Dixit, V.M. (1998) An induced proximity model for caspase-8 activation. J. Biol. Chem., 273, 2926–2930.
- Wang, J., Chun, H.J., Wong, W., Spencer, D.M., and Lenardo, M.J. (2001) Caspase-10 is an initiator caspase in death receptor signaling. Proc. Natl. Acad. Sci. U.S.A., 98, 13884–13888.
- Sprick, M.R., Rieser, E., Stahl, H., Grosse-Wilde, A., Weigand, M.A., and Walczak, H. (2002) Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. EMBO J., 21, 4520–4530.
- Barnhart, B.C., Alappat, E.C., and Peter, M.E. (2003) The CD95 type I/type II model. Semin. Immunol., 15, 185–193.
- Li, H., Zhu, H., Xu, C.J., and Yuan, J. (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the fas pathway of apoptosis. Cell, 94, 491–501.
- Tait, S.W. and Green, D.R. (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol., 11, 621–632.
- Kroemer, G., Galluzzi, L., and Brenner, C. (2007) Mitochondrial membrane permeabilization in cell death. Physiol. Rev., 87, 99–163.
- Chipuk, J.E., Moldoveanu, T., Llambi, F., Parsons, M.J., and Green, D.R. (2010) The BCL-2 family reunion. Mol. Cell, 37, 299–310.
- Ren, D., Tu, H.C., Kim, H., Wang, G.X., Bean, G.R., Takeuchi, O., Jeffers, J.R., Zambetti, G.P., Hsieh, J.J., and Cheng, E.H. (2010) BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science, 330, 1390–1393.
- Renault, T.T., Floros, K.V., and Chipuk, J.E. (2013) BAK/BAX activation and cytochrome c release assays using isolated mitochondria. Methods, 61, 146–155.
- Westphal, D., Dewson, G., Czabotar, P.E., and Kluck, R.M. (2011) Molecular biology of bax and bak activation and action. Biochim. Biophys. Acta, 1813, 521–531.
- Zou, H., Henzel, W.J., Liu, X., Lutschg, A., and Wang, X. (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell, 90, 405–413.
- Acehan, D., Jiang, X., Morgan, D.G., Heuser, J.E., Wang, X., and Akey, C.W. (2002) Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol. Cell, 9, 423–432.
- Kuida, K., Haydar, T.F., Kuan, C.Y., Gu, Y., Taya, C., Karasuyama, H., Su, M.S., Rakic, P., and Flavell, R.A. (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell, 94, 325–337.
- Malladi, S., Challa-Malladi, M., Fearnhead, H.O., and Bratton, S.B. (2009) The apaf-1*procaspase-9 apoptosome complex functions as a proteolytic-based molecular timer. EMBO J., 28, 1916–1925.
- Westphal, D., Kluck, R.M., and Dewson, G. (2014) Building blocks of the apoptotic pore: how bax and bak are activated and oligomerize during apoptosis. Cell Death Differ., 21, 196–205.
- Lopez-Otin, C. and Hunter, T. (2010) The regulatory crosstalk between kinases and proteases in cancer. Nat. Rev. Cancer, 10, 278–292.
- Cardone, M.H., Roy, N., Stennicke, H.R., Salvesen, G.S., Franke, T.F., Stanbridge, E., Frisch, S., and Reed, J.C. (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science, 282, 1318–1321.
- Peng, C., Cho, Y.Y., Zhu, F., Zhang, J., Wen, W., Xu, Y., Yao, K., Ma, W.Y., Bode, A.M., and Dong, Z. (2011) Phosphorylation of caspase-8 (thr-263) by ribosomal S6 kinase 2 (RSK2) mediates caspase-8 ubiquitination and stability. J. Biol. Chem., 286, 6946–6954.
- Raina, D., Pandey, P., Ahmad, R., Bharti, A., Ren, J., Kharbanda, S., Weichselbaum, R., and Kufe, D. (2005) c-abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage. J. Biol. Chem., 280, 11147–11151.
- Voss, O.H., Kim, S., Wewers, M.D., and Doseff, A.I. (2005) Regulation of monocyte apoptosis by the protein kinase cdelta-dependent phosphorylation of caspase-3. J. Biol. Chem., 280, 17371–17379.
- Matthess, Y., Raab, M., Sanhaji, M., Lavrik, I.N., and Strebhardt, K. (2010) Cdk1/cyclin B1 controls fas-mediated apoptosis by regulating caspase-8 activity. Mol. Cell. Biol., 30, 5726–5740.
- Alvarado-Kristensson, M., Melander, F., Leandersson, K., Ronnstrand, L., Wernstedt, C., and Andersson, T. (2004) p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils. J. Exp. Med., 199, 449–458.
- Senft, J., Helfer, B., and Frisch, S.M. (2007) Caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motility. Cancer Res., 67, 11505–11509.
- Jia, S.H., Parodo, J., Kapus, A., Rotstein, O.D., and Marshall, J.C. (2008) Dynamic regulation of neutrophil survival through tyrosine phosphorylation or dephosphorylation of caspase-8. J. Biol. Chem., 283, 5402–5413.
- Cursi, S., Rufini, A., Stagni, V., Condo, I., Matafora, V., Bachi, A., Bonifazi, A.P., Coppola, L., Superti-Furga, G., Testi, R., and Barila, D. (2006) Src kinase phosphorylates caspase-8 on Tyr380: a novel mechanism of apoptosis suppression. EMBO J., 25, 1895–1905.
- Allan, L.A. and Clarke, P.R. (2007) Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis. Mol. Cell, 26, 301–310.
- McDonnell, M.A., Abedin, M.J., Melendez, M., Platikanova, T.N., Ecklund, J.R., Ahmed, K., and Kelekar, A. (2008) Phosphorylation of murine caspase-9 by the protein kinase casein kinase 2 regulates its cleavage by caspase-8. J. Biol. Chem., 283, 20149–20158.
- Seifert, A., Allan, L.A., and Clarke, P.R. (2008) DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine. FEBS J., 275, 6268–6280.
- Allan, L.A., Morrice, N., Brady, S., Magee, G., Pathak, S., and Clarke, P.R. (2003) Inhibition of caspase-9 through phosphorylation at thr 125 by ERK MAPK. Nat. Cell Biol., 5, 647–654.
- Seifert, A. and Clarke, P.R. (2009) p38alpha- and DYRK1A-dependent phosphorylation of caspase-9 at an inhibitory site in response to hyperosmotic stress. Cell. Signal., 21, 1626–1633.
- Brady, S.C., Allan, L.A., and Clarke, P.R. (2005) Regulation of caspase 9 through phosphorylation by protein kinase C zeta in response to hyperosmotic stress. Mol. Cell. Biol., 25, 10543–10555.
- Li, X., Wen, W., Liu, K., Zhu, F., Malakhova, M., Peng, C., Li, T., Kim, H.G., Ma, W., Cho, Y.Y., Bode, A.M., Dong, Z., and Dong, Z. (2011) Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines. J. Biol. Chem., 286, 22291–22299.
- Martin, M.C., Allan, L.A., Lickrish, M., Sampson, C., Morrice, N., and Clarke, P.R. (2005) Protein kinase A regulates caspase-9 activation by apaf-1 downstream of cytochrome c. J. Biol. Chem., 280, 15449–15455.
- Scaffidi, C., Medema, J.P., Krammer, P.H., and Peter, M.E. (1997) FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J. Biol. Chem., 272, 26953–26958.
- Arntzen, M.O. and Thiede, B. (2012) ApoptoProteomics, an integrated database for analysis of proteomics data obtained from apoptotic cells. Mol. Cell. Proteomics, 11, M111.010447.
- Crawford, E.D. and Wells, J.A. (2011) Caspase substrates and cellular remodeling. Annu. Rev. Biochem., 80, 1055–1087.
- Dix, M.M., Simon, G.M., and Cravatt, B.F. (2008) Global mapping of the topography and magnitude of proteolytic events in apoptosis. Cell, 134, 679–691.
- Luo, X., Budihardjo, I., Zou, H., Slaughter, C., and Wang, X. (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell, 94, 481–490.
- Desagher, S., Osen-Sand, A., Montessuit, S., Magnenat, E., Vilbois, F., Hochmann, A., Journot, L., Antonsson, B., and Martinou, J.C. (2001) Phosphorylation of bid by casein kinases I and II regulates its cleavage by caspase 8. Mol. Cell, 8, 601–611.
- Wang, K., Yin, X.M., Chao, D.T., Milliman, C.L., and Korsmeyer, S.J. (1996) BID: a novel BH3 domain-only death agonist. Genes Dev., 10, 2859–2869.
- Turowec, J.P., Duncan, J.S., Gloor, G.B., and Litchfield, D.W. (2011) Regulation of caspase pathways by protein kinase CK2: identification of proteins with overlapping CK2 and caspase consensus motifs. Mol. Cell. Biochem., 356, 159–167.
- Litchfield, D.W. (2003) Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem. J., 369, 1–15.
- Torres, J., Rodriguez, J., Myers, M.P., Valiente, M., Graves, J.D., Tonks, N.K., and Pulido, R. (2003) Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3: implications for the control of protein stability and PTEN-protein interactions. J. Biol. Chem., 278, 30652–30660.
- Kitamura, D., Kaneko, H., Miyagoe, Y., Ariyasu, T., and Watanabe, T. (1989) Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage. Nucleic Acids Res., 17, 9367–9379.
- Ruzzene, M., Brunati, A.M., Sarno, S., Donella-Deana, A., and Pinna, L.A. (1999) Hematopoietic lineage cell specific protein 1 associates with and down-regulates protein kinase CK2. FEBS Lett., 461, 32–36.
- Ruzzene, M., Brunati, A.M., Sarno, S., Marin, O., Donella-Deana, A., and Pinna, L.A. (2000) Ser/Thr phosphorylation of hematopoietic specific protein 1 (HS1): implication of protein kinase CK2. Eur. J. Biochem./FEBS, 267, 3065–3072.
- Ruzzene, M., Penzo, D., and Pinna, L.A. (2002) Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in jurkat cells. Biochem. J., 364, 41–47.
- Yin, X., Gu, S., and Jiang, J.X. (2001) The development-associated cleavage of lens connexin 45.6 by caspase-3-like protease is regulated by casein kinase II-mediated phosphorylation. J. Biol. Chem., 276, 34567–34572.
- Koseki, T., Inohara, N., Chen, S., and Nunez, G. (1998) ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases. Proc. Natl. Acad. Sci. U.S.A., 95, 5156–5160.
- Li, P.F., Li, J., Muller, E.C., Otto, A., Dietz, R., and von Harsdorf, R. (2002) Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC. Mol. Cell, 10, 247–258.
- Austen, M., Luscher, B., and Luscher-Firzlaff, J.M. (1997) Characterization of the transcriptional regulator YY1. the bipartite transactivation domain is independent of interaction with the TATA box-binding protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding protein (CPB)-binding protein. J. Biol. Chem., 272, 1709–1717.
- Gordon, S., Akopyan, G., Garban, H., and Bonavida, B. (2006) Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene, 25, 1125–1142.
- Shi, Y., Lee, J.S., and Galvin, K.M. (1997) Everything you have ever wanted to know about Yin Yang 1. Biochim. Biophys. Acta, 1332, F49–F66.
- Riman, S., Rizkallah, R., Kassardjian, A., Alexander, K.E., Luscher, B., and Hurt, M.M. (2012) Phosphorylation of the transcription factor YY1 by CK2alpha prevents cleavage by caspase 7 during apoptosis. Mol. Cell. Biol., 32, 797–807.
- Griner, E.M. and Kazanietz, M.G. (2007) Protein kinase C and other diacylglycerol effectors in cancer. Nat. Rev. Cancer, 7, 281–294.
- Emoto, Y., Manome, Y., Meinhardt, G., Kisaki, H., Kharbanda, S., Robertson, M., Ghayur, T., Wong, W.W., Kamen, R., and Weichselbaum, R. (1995) Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells. EMBO J., 14, 6148–6156.
- Ghayur, T., Hugunin, M., Talanian, R.V., Ratnofsky, S., Quinlan, C., Emoto, Y., Pandey, P., Datta, R., Huang, Y., Kharbanda, S., Allen, H., Kamen, R., Wong, W., and Kufe, D. (1996) Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis. J. Exp. Med., 184, 2399–2404.
- Lu, W., Lee, H.K., Xiang, C., Finniss, S., and Brodie, C. (2007) The phosphorylation of tyrosine 332 is necessary for the caspase 3-dependent cleavage of PKCdelta and the regulation of cell apoptosis. Cell. Signal., 19, 2165–2173.
- Cha, H., Smith, B.L., Gallo, K., Machamer, C.E., and Shapiro, P. (2004) Phosphorylation of golgin-160 by mixed lineage kinase 3. J. Cell Sci., 117, 751–760.
- Mancini, M., Machamer, C.E., Roy, S., Nicholson, D.W., Thornberry, N.A., Casciola-Rosen, L.A., and Rosen, A. (2000) Caspase-2 is localized at the golgi complex and cleaves golgin-160 during apoptosis. J. Cell Biol., 149, 603–612.
- Hicks, S.W. and Machamer, C.E. (2002) The NH2-terminal domain of golgin-160 contains both golgi and nuclear targeting information. J. Biol. Chem., 277, 35833–35839.
- Di Bacco, A.M. and Cotter, T.G. (2002) p53 expression in K562 cells is associated with caspase-mediated cleavage of c-ABL and BCR-ABL protein kinases. Br. J. Haematol., 117, 588–597.
- Barila, D., Rufini, A., Condo, I., Ventura, N., Dorey, K., Superti-Furga, G., and Testi, R. (2003) Caspase-dependent cleavage of c-abl contributes to apoptosis. Mol. Cell. Biol., 23, 2790–2799.
- Machuy, N., Rajalingam, K., and Rudel, T. (2004) Requirement of caspase-mediated cleavage of c-abl during stress-induced apoptosis. Cell Death Differ., 11, 290–300.
- Okita, N., Kudo, Y., and Tanuma, S. (2007) Checkpoint kinase 1 is cleaved in a caspase-dependent pathway during genotoxic stress-induced apoptosis. Biol. Pharm. Bull., 30, 359–362.
- Matsuura, K., Wakasugi, M., Yamashita, K., and Matsunaga, T. (2008) Cleavage-mediated activation of Chk1 during apoptosis. J. Biol. Chem., 283, 25485–25491.
- Graves, J.D., Gotoh, Y., Draves, K.E., Ambrose, D., Han, D.K., Wright, M., Chernoff, J., Clark, E.A., and Krebs, E.G. (1998) Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J., 17, 2224–2234.
- Kakeya, H., Onose, R., and Osada, H. (1998) Caspase-mediated activation of a 36-kDa myelin basic protein kinase during anticancer drug-induced apoptosis. Cancer Res., 58, 4888–4894.
- Lee, K.K., Murakawa, M., Nishida, E., Tsubuki, S., Kawashima, S., Sakamaki, K., and Yonehara, S. (1998) Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis. Oncogene, 16, 3029–3037.
- Lee, K.K., Ohyama, T., Yajima, N., Tsubuki, S., and Yonehara, S. (2001) MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. J. Biol. Chem., 276, 19276–19285.
- Song, J.J. and Lee, Y.J. (2008) Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily. Cell. Signal., 20, 892–906.
- Lee, N., MacDonald, H., Reinhard, C., Halenbeck, R., Roulston, A., Shi, T., and Williams, L.T. (1997) Activation of hPAK65 by caspase cleavage induces some of the morphological and biochemical changes of apoptosis. Proc. Natl. Acad. Sci. U.S.A., 94, 13642–13647.
- Rudel, T. and Bokoch, G.M. (1997) Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science, 276, 1571–1574.
- Vilas, G.L., Corvi, M.M., Plummer, G.J., Seime, A.M., Lambkin, G.R., and Berthiaume, L.G. (2006) Posttranslational myristoylation of caspase-activated p21-activated protein kinase 2 (PAK2) potentiates late apoptotic events. Proc. Natl. Acad. Sci. U.S.A., 103, 6542–6547.
- Jakobi, R., McCarthy, C.C., Koeppel, M.A., and Stringer, D.K. (2003) Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation. J. Biol. Chem., 278, 38675–38685.
- Fischer, U., Stroh, C., and Schulze-Osthoff, K. (2006) Unique and overlapping substrate specificities of caspase-8 and caspase-10. Oncogene, 25, 152–159.
- DeVries, T.A., Neville, M.C., and Reyland, M.E. (2002) Nuclear import of PKCdelta is required for apoptosis: identification of a novel nuclear import sequence. EMBO J., 21, 6050–6060.
- Sitailo, L.A., Tibudan, S.S., and Denning, M.F. (2006) The protein kinase C delta catalytic fragment targets mcl-1 for degradation to trigger apoptosis. J. Biol. Chem., 281, 29703–29710.
- Panaretakis, T., Laane, E., Pokrovskaja, K., Bjorklund, A.C., Moustakas, A., Zhivotovsky, B., Heyman, M., Shoshan, M.C., and Grander, D. (2005) Doxorubicin requires the sequential activation of caspase-2, protein kinase cdelta, and c-jun NH2-terminal kinase to induce apoptosis. Mol. Biol. Cell, 16, 3821–3831.
- Sebbagh, M., Renvoize, C., Hamelin, J., Riche, N., Bertoglio, J., and Breard, J. (2001) Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat. Cell Biol., 3, 346–352.
- Coleman, M.L., Sahai, E.A., Yeo, M., Bosch, M., Dewar, A., and Olson, M.F. (2001) Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol., 3, 339–345.
- Bachelder, R.E., Wendt, M.A., Fujita, N., Tsuruo, T., and Mercurio, A.M. (2001) The cleavage of Akt/protein kinase B by death receptor signaling is an important event in detachment-induced apoptosis. J. Biol. Chem., 276, 34702–34707.
- Xu, J., Liu, D., and Songyang, Z. (2002) The role of asp-462 in regulating akt activity. J. Biol. Chem., 277, 35561–35566.
- Widmann, C., Gerwins, P., Johnson, N.L., Jarpe, M.B., and Johnson, G.L. (1998) MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis. Mol. Cell. Biol., 18, 2416–2429.
- Bachelder, R.E., Ribick, M.J., Marchetti, A., Falcioni, R., Soddu, S., Davis, K.R., and Mercurio, A.M. (1999) p53 inhibits alpha 6 beta 4 integrin survival signaling by promoting the caspase 3-dependent cleavage of AKT/PKB. J. Cell Biol., 147, 1063–1072.
- Asselin, E., Mills, G.B., and Tsang, B.K. (2001) XIAP regulates akt activity and caspase-3-dependent cleavage during cisplatin-induced apoptosis in human ovarian epithelial cancer cells. Cancer Res., 61, 1862–1868.
- Jahani-Asl, A., Basak, A., and Tsang, B.K. (2007) Caspase-3-mediated cleavage of akt: involvement of non-consensus sites and influence of phosphorylation. FEBS Lett., 581, 2883–2888.
- Tikhomirov, O. and Carpenter, G. (2001) Caspase-dependent cleavage of ErbB-2 by geldanamycin and staurosporin. J. Biol. Chem., 276, 33675–33680.
- Tikhomirov, O., Dikov, M., and Carpenter, G. (2005) Identification of proteolytic fragments from ErbB-2 that induce apoptosis. Oncogene, 24, 3906–3913.
- Benoit, V., Chariot, A., Delacroix, L., Deregowski, V., Jacobs, N., Merville, M.P., and Bours, V. (2004) Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression. Cancer Res., 64, 2684–2691.
- Strohecker, A.M., Yehiely, F., Chen, F., and Cryns, V.L. (2008) Caspase cleavage of HER-2 releases a bad-like cell death effector. J. Biol. Chem., 283, 18269–18282.
- Wen, L.P., Fahrni, J.A., Troie, S., Guan, J.L., Orth, K., and Rosen, G.D. (1997) Cleavage of focal adhesion kinase by caspases during apoptosis. J. Biol. Chem., 272, 26056–26061.
- Gervais, F.G., Thornberry, N.A., Ruffolo, S.C., Nicholson, D.W., and Roy, S. (1998) Caspases cleave focal adhesion kinase during apoptosis to generate a FRNK-like polypeptide. J. Biol. Chem., 273, 17102–17108.
- Levkau, B., Herren, B., Koyama, H., Ross, R., and Raines, E.W. (1998) Caspase-mediated cleavage of focal adhesion kinase pp125FAK and disassembly of focal adhesions in human endothelial cell apoptosis. J. Exp. Med., 187, 579–586.
- Crouch, D.H., Fincham, V.J., and Frame, M.C. (1996) Targeted proteolysis of the focal adhesion kinase pp125 FAK during c-MYC-induced apoptosis is suppressed by integrin signalling. Oncogene, 12, 2689–2696.
- Lin, Y., Devin, A., Rodriguez, Y., and Liu, Z.G. (1999) Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev., 13, 2514–2526.
- Kim, J.W., Choi, E.J., and Joe, C.O. (2000) Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP. Oncogene, 19, 4491–4499.
- Hall, A. (1998) Rho GTPases and the actin cytoskeleton. Science, 279, 509–514.
- Neves, S.R., Ram, P.T., and Iyengar, R. (2002) G protein pathways. Science, 296, 1636–1639.
- Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein rho. EMBO J., 15, 2208–2216.
- Leung, T., Chen, X.Q., Manser, E., and Lim, L. (1996) The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol. Cell. Biol., 16, 5313–5327.
- Ishizaki, T., Maekawa, M., Fujisawa, K., Okawa, K., Iwamatsu, A., Fujita, A., Watanabe, N., Saito, Y., Kakizuka, A., Morii, N., and Narumiya, S. (1996) The small GTP-binding protein rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J., 15, 1885–1893.
- Sekine, A., Fujiwara, M., and Narumiya, S. (1989) Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase. J. Biol. Chem., 264, 8602–8605.
- Ridley, A.J. and Hall, A. (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell, 70, 389–399.
- Nagahara, H., Vocero-Akbani, A.M., Snyder, E.L., Ho, A., Latham, D.G., Lissy, N.A., Becker-Hapak, M., Ezhevsky, S.A., and Dowdy, S.F. (1998) Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration. Nat. Med., 4, 1449–1452.
- Walter, B.N., Huang, Z., Jakobi, R., Tuazon, P.T., Alnemri, E.S., Litwack, G., and Traugh, J.A. (1998) Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). effects of autophosphorylation on activity. J. Biol. Chem., 273, 28733–28739.
- Lim, L., Manser, E., Leung, T., and Hall, C. (1996) Regulation of phosphorylation pathways by p21 GTPases. the p21 ras-related rho subfamily and its role in phosphorylation signalling pathways. Eur. J. Biochem./FEBS, 242, 171–185.
- Sells, M.A. and Chernoff, J. (1997) Emerging from the pak: the p21-activated protein kinase family. Trends Cell Biol., 7, 162–167.
- Jakobi, R., Moertl, E., and Koeppel, M.A. (2001) p21-activated protein kinase gamma-PAK suppresses programmed cell death of BALB3T3 fibroblasts. J. Biol. Chem., 276, 16624–16634.
-
Tang, T.K., Chang, W.C., Chan, W.H., Yang, S.D., Ni, M.H., and Yu, J.S. (1998) Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells. J. Cell. Biochem., 70, 442–454.
10.1002/(SICI)1097-4644(19980915)70:4<442::AID-JCB2>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- Schaller, M.D., Borgman, C.A., Cobb, B.S., Vines, R.R., Reynolds, A.B., and Parsons, J.T. (1992) pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc. Natl. Acad. Sci. U.S.A., 89, 5192–5196.
- Schaller, M.D., Borgman, C.A., and Parsons, J.T. (1993) Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. Mol. Cell. Biol., 13, 785–791.
- Schaller, M.D., Hildebrand, J.D., and Parsons, J.T. (1999) Complex formation with focal adhesion kinase: a mechanism to regulate activity and subcellular localization of src kinases. Mol. Biol. Cell, 10, 3489–3505.
- Mellor, H. and Parker, P.J. (1998) The extended protein kinase C superfamily. Biochem. J., 332 (Pt 2), 281–292.
- Zhao, M., Xia, L., and Chen, G.Q. (2012) Protein kinase cdelta in apoptosis: a brief overview. Arch. Immunol. Ther. Exp. (Warsz.), 60, 361–372.
- Humphries, M.J., Ohm, A.M., Schaack, J., Adwan, T.S., and Reyland, M.E. (2008) Tyrosine phosphorylation regulates nuclear translocation of PKCdelta. Oncogene, 27, 3045–3053.
- Bharti, A., Kraeft, S.K., Gounder, M., Pandey, P., Jin, S., Yuan, Z.M., Lees-Miller, S.P., Weichselbaum, R., Weaver, D., Chen, L.B., Kufe, D., and Kharbanda, S. (1998) Inactivation of DNA-dependent protein kinase by protein kinase cdelta: implications for apoptosis. Mol. Cell. Biol., 18, 6719–6728.
- Lee, S.J., Kim, D.C., Choi, B.H., Ha, H., and Kim, K.T. (2006) Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. J. Biol. Chem., 281, 2215–2224.
- Yoshida, K., Liu, H., and Miki, Y. (2006) Protein kinase C delta regulates Ser46 phosphorylation of p53 tumor suppressor in the apoptotic response to DNA damage. J. Biol. Chem., 281, 5734–5740.
- Yoshida, K., Wang, H.G., Miki, Y., and Kufe, D. (2003) Protein kinase cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9. EMBO J., 22, 1431–1441.
- Cross, T., Griffiths, G., Deacon, E., Sallis, R., Gough, M., Watters, D., and Lord, J.M. (2000) PKC-delta is an apoptotic lamin kinase. Oncogene, 19, 2331–2337.
- D'Costa, A.M. and Denning, M.F. (2005) A caspase-resistant mutant of PKC-delta protects keratinocytes from UV-induced apoptosis. Cell Death Differ., 12, 224–232.
- Qi, X. and Mochly-Rosen, D. (2008) The PKCdelta -abl complex communicates ER stress to the mitochondria - an essential step in subsequent apoptosis. J. Cell Sci., 121, 804–813.
- DeVries-Seimon, T.A., Ohm, A.M., Humphries, M.J., and Reyland, M.E. (2007) Induction of apoptosis is driven by nuclear retention of protein kinase C delta. J. Biol. Chem., 282, 22307–22314.
- Hellwig, C.T., Ludwig-Galezowska, A.H., Concannon, C.G., Litchfield, D.W., Prehn, J.H., and Rehm, M. (2010) Activity of protein kinase CK2 uncouples bid cleavage from caspase-8 activation. J. Cell Sci., 123, 1401–1406.
- Luthi, A.U. and Martin, S.J. (2007) The CASBAH: a searchable database of caspase substrates. Cell Death Differ., 14, 641–650.
- Ong, S.E., Blagoev, B., Kratchmarova, I., Kristensen, D.B., Steen, H., Pandey, A., and Mann, M. (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol. Cell. Proteomics, 1, 376–386.
- Kleifeld, O., Doucet, A., auf dem Keller, U., Prudova, A., Schilling, O., Kainthan, R.K., Starr, A.E., Foster, L.J., Kizhakkedathu, J.N., and Overall, C.M. (2010) Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat. Biotechnol., 28, 281–288.
- Al-Lazikani, B., Banerji, U., and Workman, P. (2012) Combinatorial drug therapy for cancer in the post-genomic era. Nat. Biotechnol., 30, 679–692.
- Crawford, E.D., Seaman, J.E., Agard, N., Hsu, G.W., Julien, O., Mahrus, S., Nguyen, H., Shimbo, K., Yoshihara, H.A., Zhuang, M., Chalkley, R.J., and Wells, J.A. (2013) The DegraBase: a database of proteolysis in healthy and apoptotic human cells. Mol. Cell. Proteomics, 12, 813–824.