Inactivation of Tumor Suppressor p53 by Mot-2, a hsp70 Family Member
The mortalin genes, mot-1 and mot-2, are hsp70 family members that were originally cloned from normal and immortal murine cells, respectively. Their proteins differ by only two amino acid residues but exhibit different subcellular localizations, arise from two distinct genes, and have contrasting bi...
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| Veröffentlicht in: | The Journal of biological chemistry 1998-11, Vol.273 (45), p.29586-29591 |
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| container_title | The Journal of biological chemistry |
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| creator | Wadhwa, Renu Takano, Syuichi Robert, Martin Yoshida, Akiko Nomura, Hitoshi Reddel, Roger R. Mitsui, Youji Kaul, Sunil C. |
| description | The mortalin genes, mot-1 and mot-2, are hsp70 family members that were originally cloned from normal and immortal murine cells, respectively. Their proteins differ by only two amino acid residues but exhibit different subcellular localizations, arise from two distinct genes, and have contrasting biological activities. We report here that the two proteins also differ in their interactions with the tumor suppressor protein p53. The pancytosolic mot-1 protein in normal cells did not show colocalization with p53; in contrast, nonpancytosolic mot-2 and p53 overlapped significantly in immortal cells. Transfection of mot-2 but not mot-1 resulted in the repression of p53-mediated transactivation in p53-responsive reporter assays. Inactivation of p53 by mot-2 was supported by the down-regulation of p53-responsive genes p21WAF-1 and mdm-2 in mot-2-transfected cells only. Furthermore, NIH 3T3 cells transfected with expression plasmid encoding green fluorescent protein-taggedmot-2 but not mot-1 showed an abrogation of nuclear translocation of wild-type p53. These results demonstrate a novel mechanism of p53 inactivation by mot-2 protein. |
| doi_str_mv | 10.1074/jbc.273.45.29586 |
| format | Article |
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Their proteins differ by only two amino acid residues but exhibit different subcellular localizations, arise from two distinct genes, and have contrasting biological activities. We report here that the two proteins also differ in their interactions with the tumor suppressor protein p53. The pancytosolic mot-1 protein in normal cells did not show colocalization with p53; in contrast, nonpancytosolic mot-2 and p53 overlapped significantly in immortal cells. Transfection of mot-2 but not mot-1 resulted in the repression of p53-mediated transactivation in p53-responsive reporter assays. Inactivation of p53 by mot-2 was supported by the down-regulation of p53-responsive genes p21WAF-1 and mdm-2 in mot-2-transfected cells only. Furthermore, NIH 3T3 cells transfected with expression plasmid encoding green fluorescent protein-taggedmot-2 but not mot-1 showed an abrogation of nuclear translocation of wild-type p53. These results demonstrate a novel mechanism of p53 inactivation by mot-2 protein.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.273.45.29586</identifier><identifier>PMID: 9792667</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3T3 Cells ; Animals ; Biological Transport ; Cell Nucleus - metabolism ; Down-Regulation - physiology ; Fluorescent Antibody Technique ; HSP70 Heat-Shock Proteins - physiology ; Mice ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>The Journal of biological chemistry, 1998-11, Vol.273 (45), p.29586-29591</ispartof><rights>1998 © 1998 ASBMB. 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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 3T3 Cells Animals Biological Transport Cell Nucleus - metabolism Down-Regulation - physiology Fluorescent Antibody Technique HSP70 Heat-Shock Proteins - physiology Mice Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism |
| title | Inactivation of Tumor Suppressor p53 by Mot-2, a hsp70 Family Member |
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