PHAPI/pp32 suppresses tumorigenesis by stimulating Apoptosis Journal Article
| Authors: | Pan, W.; da Graca, L. S.; Shao, Y.; Yin, Q.; Wu, H.; Jiang, X. |
| Article Title: | PHAPI/pp32 suppresses tumorigenesis by stimulating Apoptosis |
| Abstract: | PHAPI/pp32 is a tumor suppressor whose expression is altered in various human cancers. Although PHAPI possesses multiple biochemical activities, the molecular basis for its tumor-suppressive function has remained obscure. Recently we identified PHAPI as an apoptotic enhancer that stimulates apoptosome-mediated caspase activation. In this study, we defined the structural requirement for its activity to stimulate caspase activation using a series of truncation mutants of PHAPI. Further, utilizing these mutants, we provide evidence to support the model that the apoptotic activity of PHAPI is required for its tumor-suppressive capability. Consistently, pp32R1, a close homolog of PHAPI and yet an oncoprotein, is not able to stimulate caspase activation. A highly discrete region between these two proteins localizes to an essential caspase activation motif of PHAPI. Additionally, PHAPI is predominantly a nuclear protein, and it can translocate to the cytoplasm during apoptosis. Disruption of the nuclear localization signal of PHAPI caused a modest decrease of its tumor-suppressive function, indicating that nuclear localization of PHAPI contributes to, but is not essential for, tumor suppression. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; unclassified drug; oncoprotein; human cell; genetics; mutation; mutant protein; protein function; protein localization; protein motif; mouse; animal; metabolism; animals; mice; cell death; apoptosis; nuclear protein; enzyme activation; caspase; hela cell; caspases; hela cells; tumorigenesis; cell transformation, neoplastic; nuclear proteins; cancer inhibition; tumors; cell transformation; gene disruption; signal peptide; intracellular signaling peptides and proteins; tumor suppressor proteins; protein transport; phosphoproteins; cell nucleus; protein structure; tumor suppressor protein; nuclear localization signal; phosphoprotein; amino acid motifs; human cancer; apoptosome; apoptotic; apoptotic activity; biochemical activity; caspase activation; discrete regions; molecular basis; nuclear localization; structural requirements; truncation mutants; tumor suppression; tumor suppressors; evolutionary algorithms; protein phapi; putative hla associated protein 1; anp32a protein, human; apoptosis inducing factor; phosphoprotein 32; structural homology; nuclear localization signals |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 284 |
| Issue: | 11 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2009-03-13 |
| Start Page: | 6946 |
| End Page: | 6954 |
| Language: | English |
| DOI: | 10.1074/jbc.M805801200 |
| PUBMED: | 19121999 |
| PROVIDER: | scopus |
| PMCID: | PMC2652289 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: JBCHA" - "Source: Scopus" |
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