The Mechanism of p53 Rescue by SUSP4
Do-Hyoung Kim
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Chewook Lee
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Si-Hyung Lee
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
These authors contributed equally to this work.
Search for more papers by this authorProf. Kyung-Tae Kim
Molecular Epidemology Branch, Research Institute National Cancer Center, 323 Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408 Korea
These authors contributed equally to this work.
Search for more papers by this authorJoan J. Han
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
College of Human Medicine, Michigan State University, East Lansing, MI, 48824 USA
Search for more papers by this authorEun-Ji Cha
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Search for more papers by this authorJi-Eun Lim
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Search for more papers by this authorYe-Jin Cho
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Department of Bioinformatics, University of Science and Technology, 217, Gajeong-ro, Yuseong-gu, Daejoen, 34113 Korea
Search for more papers by this authorProf. Seung-Hee Hong
Division of Food Science and Culinary Art, Food and Nutrition Major, Shinhan University, 95 Hoam-ro, Uijeongbu-si, Gyeonggi-do, 11644 Korea
Search for more papers by this authorCorresponding Author
Dr. Kyou-Hoon Han
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Department of Bioinformatics, University of Science and Technology, 217, Gajeong-ro, Yuseong-gu, Daejoen, 34113 Korea
Search for more papers by this authorDo-Hyoung Kim
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Chewook Lee
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Si-Hyung Lee
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
These authors contributed equally to this work.
Search for more papers by this authorProf. Kyung-Tae Kim
Molecular Epidemology Branch, Research Institute National Cancer Center, 323 Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408 Korea
These authors contributed equally to this work.
Search for more papers by this authorJoan J. Han
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
College of Human Medicine, Michigan State University, East Lansing, MI, 48824 USA
Search for more papers by this authorEun-Ji Cha
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Search for more papers by this authorJi-Eun Lim
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Search for more papers by this authorYe-Jin Cho
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Department of Bioinformatics, University of Science and Technology, 217, Gajeong-ro, Yuseong-gu, Daejoen, 34113 Korea
Search for more papers by this authorProf. Seung-Hee Hong
Division of Food Science and Culinary Art, Food and Nutrition Major, Shinhan University, 95 Hoam-ro, Uijeongbu-si, Gyeonggi-do, 11644 Korea
Search for more papers by this authorCorresponding Author
Dr. Kyou-Hoon Han
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea
Department of Bioinformatics, University of Science and Technology, 217, Gajeong-ro, Yuseong-gu, Daejoen, 34113 Korea
Search for more papers by this authorAbstract
p53 is an important tumor-suppressor protein deactivation of which by mdm2 results in cancers. A SUMO-specific protease 4 (SUSP4) was shown to rescue p53 from mdm2-mediated deactivation, but the mechanism is unknown. The discovery by NMR spectroscopy of a “p53 rescue motif” in SUSP4 that disrupts p53-mdm2 binding is presented. This 29-residue motif is pre-populated with two transient helices connected by a hydrophobic linker. The helix at the C-terminus binds to the well-known p53-binding pocket in mdm2 whereas the N-terminal helix serves as an affinity enhancer. The hydrophobic linker binds to a previously unidentified hydrophobic crevice in mdm2. Overall, SUSP4 appears to use two synergizing modules, the p53 rescue motif described here and a globular-structured SUMO-binding catalytic domain, to stabilize p53. A p53 rescue motif peptide exhibits an anti-tumor activity in cancer cell lines expressing wild-type p53. A pre-structures motif in the intrinsically disordered proteins is thus important for target recognition.
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