Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member

Renu Wadhwa, Syuichi Takano, Martin Robert, Akiko Yoshida, Hitoshi Nomura, Roger R. Reddel, Youji Mitsui, Sunil C. Kaul

研究成果: Article査読

194 被引用数 (Scopus)

抄録

The mortalin genes, met-1 and met-2, are hsp70 family members that were originally cloned from normal and immortal murine cells, respectively. Their proteins differ by only two amine 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 met-2 and p53 overlapped significantly in immortal cells. Transfection of met-2 but not met-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 p21(WAF-1) and mdm-2 in mot-2-transfected cells only. Furthermore, NIH 3T3 cells transfected with expression plasmid encoding green fluorescent protein-tagged mot-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.

本文言語English
ページ(範囲)29586-29591
ページ数6
ジャーナルJournal of Biological Chemistry
273
45
DOI
出版ステータスPublished - 1998 11 6
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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