Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 15 January 2002
Vol. 2002, Issue 115, p. tw25
[DOI: 10.1126/stke.2002.115.tw25]

EDITORS' CHOICE

Apoptosis Controlled by a WISP

Wnt1-induced secreted protein (WISP-1) is a member of the CCN family of growth factors [named for the founding members (connective tissue growth factor, cysteine rich-61, and nephroblastoma overexpressed)], which are secreted cysteine-rich, heparin-binding, and extracellular matrix-associated proteins. Su et al. showed that WISP-1 activated the serine-threonine protein kinase Akt, which has been implicated in cell survival pathways. Overexpression of WISP-1 inhibited apoptosis after treatments that induced DNA damage and produced a death signal dependent on the tumor suppressor and transcriptional regulator p53. WISP-1 did not promote cell survival when expressed with dominant-negative mutants of Akt or in cells deficient in p53. Protection by WISP-1 was specific for stimuli that activated apoptosis through the "intrinsic" pathway by release of cytochrome c from the mitochondria, and WISP-1 was ineffective for protecting cells from apoptosis due to activation of the death receptor Fas. Overexpression of WISP-1 did not appear to inhibit p53 activation or transcriptional activity directly. Instead, WISP-1-overexpressing cells expressed larger amounts of the anti-apoptotic protein Bcl-XL at rest than untransfected cells did, and cytochrome c release was inhibited in the WISP-1-overexpressing cells when they were subjected to DNA-damaging stimuli. Thus, WISP-1 is a growth factor that can trigger signals that inhibit cell death in response to internal signals.

F. Su, M. Overholtzer, D. Besser, A. J. Levine, WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of Akt kinase. Genes Dev. 16, 46-57 (2002). [Abstract] [Full Text]

Citation: Controlled by a WISP. Sci. STKE 2002, tw25 (2002).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882