Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member
- PMID: 9792667
- DOI: 10.1074/jbc.273.45.29586
Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member
Abstract
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 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.
Similar articles
-
Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy.Future Med Chem. 2023 Nov;15(22):2087-2112. doi: 10.4155/fmc-2023-0061. Epub 2023 Oct 25. Future Med Chem. 2023. PMID: 37877348 Review.
-
Functional significance of minor structural and expression changes in stress chaperone mortalin.Ann N Y Acad Sci. 2007 Nov;1119:165-75. doi: 10.1196/annals.1404.007. Ann N Y Acad Sci. 2007. PMID: 18056964 Review.
-
Transcriptional inactivation of p53 by deletions and single amino acid changes in mouse mot-1 protein.Biochem Biophys Res Commun. 2000 Dec 20;279(2):602-6. doi: 10.1006/bbrc.2000.3986. Biochem Biophys Res Commun. 2000. PMID: 11118332
-
NIH 3T3 cells malignantly transformed by mot-2 show inactivation and cytoplasmic sequestration of the p53 protein.Cell Res. 1999 Dec;9(4):261-9. doi: 10.1038/sj.cr.7290025. Cell Res. 1999. PMID: 10628835
-
Malignant transformation of NIH3T3 cells by overexpression of mot-2 protein.Oncogene. 1998 Aug 20;17(7):907-11. doi: 10.1038/sj.onc.1202017. Oncogene. 1998. PMID: 9780007
Cited by
-
Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy.Cancer Res Commun. 2023 Jul 27;3(7):1378-1396. doi: 10.1158/2767-9764.CRC-23-0111. eCollection 2023 Jul. Cancer Res Commun. 2023. PMID: 37520743 Free PMC article.
-
Identification of a new member of Mortaparib class of inhibitors that target mortalin and PARP1.Front Cell Dev Biol. 2022 Sep 12;10:918970. doi: 10.3389/fcell.2022.918970. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36172283 Free PMC article.
-
Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53Ser46 mutant.Curr Res Struct Biol. 2022 Sep 13;4:320-331. doi: 10.1016/j.crstbi.2022.09.002. eCollection 2022. Curr Res Struct Biol. 2022. PMID: 36164647 Free PMC article.
-
The mitochondrial unfolded protein response (UPRmt): shielding against toxicity to mitochondria in cancer.J Hematol Oncol. 2022 Jul 21;15(1):98. doi: 10.1186/s13045-022-01317-0. J Hematol Oncol. 2022. PMID: 35864539 Free PMC article. Review.
-
Why is Mortalin a Potential Therapeutic Target for Cancer?Front Cell Dev Biol. 2022 Jun 29;10:914540. doi: 10.3389/fcell.2022.914540. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35859897 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous