title: Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein.
abstract: 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.
authors.affiliation: Chugai Research Institute for Medical Sciences, 153-2 Nagai, Niihari Mura, Ibaraki, 300-41, Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Md K
authors.initials: MK
authors.lastname: Hasan
authors.forename: Youji
authors.initials: Y
authors.lastname: Mitsui
authors.forename: Roger R
authors.initials: RR
authors.lastname: Reddel
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D019556:COS Cells; D002451:Cell Compartmentation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D024101:Mitochondrial Proteins; D009154:Mutation / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; C115087:Hspa9-ps1 protein, mouse; D024101:Mitochondrial Proteins; D016159:Tumor Suppressor Protein p53