TY - JOUR
T1 - Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member
AU - Wadhwa, Renu
AU - Takano, Syuichi
AU - Robert, Martin
AU - Yoshida, Akiko
AU - Nomura, Hitoshi
AU - Reddel, Roger R.
AU - Mitsui, Youji
AU - Kaul, Sunil C.
PY - 1998/11/6
Y1 - 1998/11/6
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.273.45.29586
DO - 10.1074/jbc.273.45.29586
M3 - Article
C2 - 9792667
AN - SCOPUS:0032491426
VL - 273
SP - 29586
EP - 29591
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 45
ER -