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, 25 June 2002
Vol. 2002, Issue 138, p. tw223
[DOI: 10.1126/stke.2002.138.tw223]


Apoptosis Broadening TRAIL's Targets

Identifying agents that destroy tumor cells but leave normal cells unharmed is a major goal in developing effective cancer treatments. The cytokine TRAIL, a member of the tumor necrosis family, has shown such potential, as it preferentially induces apoptosis of cancer cells. Now, Kim et al. report a potential mechanism to expand the range of TRAIL cancer targets. Agonists for a nuclear receptor called peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) sensitized tumor cells that are normally not responsive to TRAIL such that TRAIL did induce apoptosis. Although neither the PPAR{gamma} modulators nor TRAIL alone killed these tumor cells, combined treatment did. Furthermore, the combination did not kill normal cells. The mechanism appears not to involve PPAR{gamma}, because it persisted even in the presence of dominant-negative form of PPAR{gamma}. It seems to be mediated by the formation of a TRAIL receptor-associated signaling complex that activates the cell death program through caspase activation. A cytoplasmic protein called FLIP normally inhibits assembly of this complex, but PPAR{gamma} modulators somehow stimulate the degradation of FLIP through the ubiquitin-proteosome pathway. The cellular target of the PPAR{gamma} modulators that stimulates this proapoptotic effect has yet to be determined.

Y. Kim, N. Suh, M. Sporn, J. C. Reed, An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J. Biol. Chem. 277, 22320-22329 (2002). [Abstract] [Full Text]

Citation: Broadening TRAIL's Targets. Sci. STKE 2002, tw223 (2002).

To Advertise     Find Products

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