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WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase

Item Type:Article
Title:WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase
Creators Name:Su, F. and Overholtzer, M. and Besser, D. and Levine, A.J.
Abstract:WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway. WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich, heparin-binding, secreted proteins associated with the extracellular matrix, and can interact with cellular integrins. Expression of WISP-1 in some cells results in transformation and tumorigenesis. Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. It also is demonstrated that WISP-1 can prevent cells from undergoing apoptosis following DNA damage through inhibition of the mitochondrial release of cytochrome c and up-regulation of antiapoptotic Bcl-X(L). Furthermore, the results show that WISP-1 protects cells from p53-dependent cell death, but not Fas-ligand activated cell death, suggesting that there may be cross talk between the tumor suppressor protein p53 and WISP-1 signaling pathways. WISP-1 acts to block cell death at a late stage in the p53-mediated apoptosis pathway.
Keywords:Apoptosis, Cell Line, Cytochrome c Group, Growth Substances, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Signal Transduction, Tumor Suppressor Protein p53, bcl-X Protein, Animals
Source:Genes & Development
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:16
Number:1
Page Range:46-57
Date:2002
Official Publication:https://doi.org/10.1101/gad.942902
PubMed:View item in PubMed

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