p73β-Mediated apoptosis requires p57kip2 induction and IEX-1 inhibition Journal Article
| Authors: | Gonzalez, S.; Perez Perez, M. M.; Hernando, E.; Serrano, M.; Cordon-Cardo, C. |
| Article Title: | p73β-Mediated apoptosis requires p57kip2 induction and IEX-1 inhibition |
| Abstract: | Similarly to p53, p73α and p73β induce growth arrest and/or apoptosis in response to DNA damage or when exogenously expressed. However, how they trigger apoptosis remains unresolved. After stable transduction of either p73α or p73β, a greater apoptotic response was observed for p73β in both primary and tumor cells. Consistently, blocking ectopic and endogenous p73β expression by specific shRNA significantly decreased apoptotic levels after DNA damage. We found that p73β targets the apoptotic program at multiple levels: (i) facilitating caspase activation through p53-dependent signals and (ii) inducing p57KIP2, while down-regulating c-IPA1 and IEX1 through a p53-independent mechanism. p73β-mediated apoptosis was considerably reduced after inhibition of p57KIP2 by small interfering RNA, IEX-1 overexpression, and in mouse embryo fibroblasts derived from p57-/- mice. Data from this study offer evidence for the apoptotic activity exclusive of p73β. In the clinical context, these results might have potential therapeutic implications, because p73β could induce alternative apoptotic responses in tumors harboring p53 mutations. ©2005 American Association for Cancer Research. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; dna binding protein; human cell; genetics; dna-binding proteins; nonhuman; protein function; animal cell; mouse; animal; animals; mice; dna damage; gene; gene overexpression; apoptosis; nuclear protein; embryo; neoplasm proteins; molecular dynamics; apoptosis regulatory proteins; hct116 cells; membrane proteins; enzyme activation; caspase; transfection; physiology; nuclear proteins; gene expression regulation; tumor suppressor gene; gene expression regulation, neoplastic; biosynthesis; drug antagonism; genetic transfection; tumor suppressor proteins; membrane protein; tumor protein; tumor cell; fibroblast; protein induction; down regulation; tumor suppressor protein; immediate early protein; immediate-early proteins; short hairpin rna; genes, tumor suppressor; apoptosis regulatory protein; cell strain hct116; embryo cell; protein p73; protein p57; protein p73alpha; cyclin dependent kinase inhibitor 1c; protein p73beta; cdkn1c protein, human; cdkn1c protein, mouse; ier3 protein, human; tumor suppressor protein p73; iex 1 gene; cyclin-dependent kinase inhibitor p57 |
| Journal Title: | Cancer Research |
| Volume: | 65 |
| Issue: | 6 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-03-15 |
| Start Page: | 2186 |
| End Page: | 2192 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-04-3047 |
| PUBMED: | 15781630 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 24" - "Export Date: 24 October 2012" - "CODEN: CNREA" - "Source: Scopus" |
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