ASC is a Bax adaptor and regulates the p53–Bax mitochondrial apoptosis pathway

Speaker：趙健麟

Commentator：楊倍昌老師

Time：3/17/04 15:00-16:00

Place：Room 601

Abstract：

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a pyrin N-terminal homology domain (PYD) and caspase recruitment domain (CARD)-containing a proapoptotic molecule [1].The authors demonstrate that ASC is an adaptor protein for Bax and control P53-Bax mediated apoptosis. ASC interacted with Bax to increase translocation of Bax to mitochondria, reduction of mitochondrial membrane potential, release of cytochrom c into cytosol, which in tern activation of caspase-9, -2 and -3. Induction of ASC after treatment of genotoxic agent is p53-dependent.Small-interfering RNA (siRNA) of ASC blocked endogenous ASC expression to reduce apoptotic response and inhibited Bax translocation from cytosol to mitochondria in response to p53 or genotoxic stress, indicating that ASC play an important role in translocation of Bax to mitochondria. Thus, the results conceive that ASC can function as an adaptor for Bax and regulate p53-Bax mitochondrial pathway of apoptosis [2].

Reference：

1.     Masumoto, J. et al. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J. Biol. Chem. 274, 33825–33838 (1999).

2.     Ohtsuka, T. et al. ASC is a Bax adapt and regulates the p53–Bax mitochondrial apoptosis pathway. Nature Cell Biol. 6, 121-8 (2004)