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.

Subscribe

Sci. Signal., 5 July 2011
Vol. 4, Issue 180, p. ec184
[DOI: 10.1126/scisignal.4180ec184]

EDITORS' CHOICE

Apoptosis Evading Death

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

Upon ligation, the Fas receptor assembles the death-inducing signaling complex (DISC). The first step in the assembly of the DISC is recruitment of the adaptor protein FADD (Fas-associated death domain protein) to Fas, which in turn elicits the recruitment and activation of initiator caspases (such as caspase 8) and effector caspases (such as caspases 3 and 7). Endocytosis of Fas is also required for effective apoptotic signaling. Swindall and Bellis found that Fas was a substrate for ST6Gal-I, a glycosyltransferase that adds sialic acid to the N-glycans of glycoproteins. Increased abundance of ST6Gal-I in various cancers, including colon carcinoma, correlates with metastasis and poor prognosis. Compared with HD3 colon carcinoma cells overexpressing STGGal-I (HD3.par cells), cells depleted of ST6Gal-I by stable expression of an shRNA (HD3.sh cells) showed increased apoptosis (as assessed by activation of caspases 3 and 7, nuclear condensation, and changes in cell morphology) in response to CH11, a Fas-activating antibody, but not in response to TRAIL, the ligand for death receptor 4 (DR4) and DR5. Similarly, greater activation of caspase 3 was detected in HD3.sh cells treated with FasL, the native ligand for Fas. Overexpression of ST6Gal-I protected SW48 colon epithelial cells (in which ST6Gal-I is not detectable) from apoptosis induced by FasL but not from that induced by TRAIL. Biochemical assays indicated that Fas was sialylated by ST6Gal-I, a modification that decreased recruitment of FADD to Fas (and thus DISC formation) and prevented internalization of Fas in CH11-treated cells. Thus, the high abundance of ST6Gal-I in colon carcinoma cells may enable them to evade Fas-induced apoptosis.

A. F. Swindall, S. L. Bellis, Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells. J. Biol. Chem. 286, 22982–22990 (2011). [Abstract] [Full Text]

Citation: W. Wong, Evading Death. Sci. Signal. 4, ec184 (2011).



To Advertise     Find Products


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