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Sci. STKE, 8 April 2003
Vol. 2003, Issue 177, p. tw142
[DOI: 10.1126/stke.2003.177.tw142]


APOPTOSIS Caspase Targets c-Abl

Cells call upon the nonreceptor tyrosine kinase c-Abl to transduce signals that regulate diverse processes ranging from proliferation to apoptosis. Localization of c-Abl is crucial in determining the outcome of its activation. For example, the cell death response to tumor necrosis factor (TNF) requires c-Abl activity in the nucleus. Barila et al. report that in response to activation of the death receptor Fas, c-Abl gets cleaved in the cytoplasm by caspases, and a resulting 120-kD fragment translocates to the nucleus. This c-Abl fragment is identical in size to that generated in vitro with caspase 8 and lacks a nuclear export signal and actin binding region but retains the kinase domain, DNA-binding domains, and nuclear localization signals. Unlike wild type c-Abl, which is located in both the cytoplasm and nucleus, expression of only the 120-kD fragment in c-Abl-null cells was detected in the nucleus. Overexpression of this fragment sensitized cells to Fas-induced cell death, whereas expression of a c-Abl mutant lacking the cleavage site protected cells from apoptosis. The mechanism linking caspase-mediated cleavage to c-Abl activation remains to be determined, as cleavage did not activate c-Abl. The authors suggest that cleavage by caspases is only one step that activates the proapoptotic function of c-Abl in the nucleus.

D. Barila, A. Rufini, I. Condo, N. Ventura, K. Dorey, G. Superti-Furga, R. Testi, Caspase-dependent cleavage of c-Abl contributes to apoptosis. Mol. Cell. Biol. 23, 2790-2799 (2003). [Abstract] [Full Text]

Citation: Caspase Targets c-Abl. Sci. STKE 2003, tw142 (2003).

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