Hsp70 Family Member, mot-2/mthsp70/GRP75, Binds to the Cytoplasmic Sequestration Domain of the p53 Protein

• Published in: Experimental cell research Vol. 274; no. 2; pp. 246 - 253
• Main Authors: Wadhwa, Renu, Yaguchi, Tomoko, Hasan, Md.K., Mitsui, Youji, Reddel, Roger R., Kaul, Sunil C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2002
• Subjects: 3T3 Cells; Animals; binding domain; Binding Sites - physiology; Cell Compartmentation - physiology; Cell Nucleus - metabolism; Cell Transformation, Neoplastic - metabolism; COS Cells; Cytoplasm - metabolism; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Neoplastic - physiology; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Humans; Mice; Mitochondrial Proteins; mot-2/mthsp70; Mutation - physiology; Neoplasms - genetics; Neoplasms - metabolism; p53; Protein Structure, Tertiary - physiology; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - metabolism; binding domain; mot-2/mthsp70; p53
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.2002.5468

Hsp70 family member mot-2/mthsp70/GRP75/PBP74 was shown to bind to the tumor suppressor protein p53. In this study, by in vivo coimmunoprecipitation of mot-2 with p53 and its deletion mutants, the mot-2 binding site of p53 was mapped to its C-terminal amino acid residues 312–352, a region of p53 that includes its cytoplasmic sequestration domain. These data demonstrate that cytoplasmic sequestration and inactivation of p53 by mot-2 occurs by its binding to the cytoplasmic sequestration domain. Therefore, perturbation of mot–p53 interactions can be employed to abrogate cytoplasmic retention of wild-type p53 in tumors.