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Genes & Dev. 16 (1): 46-57

Copyright © 2002 by Cold Spring Harbor Laboratory Press.

Vol. 16, No. 1, pp. 46-57, January 1, 2002

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

Fei Su, Michael Overholtzer, Daniel Besser, and Arnold J. Levine1

Laboratory of Cancer Biology, The Rockefeller University, New York, New York 10021-6399, USA

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-XL. 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.

[Key Words: WISP-1; Akt; apoptosis; p53; DNA damage]

1 Corresponding author.

GENES & DEVELOPMENT 16:46-57 © 2002 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/02 $5.00

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