FLASH knockdown sensitizes cells to Fas-mediated apoptosis via down-regulation of the anti-apoptotic proteins, MCL-1 and Cflip short.
FLASH knockdown sensitizes cells to Fas-mediated apoptosis via down-regulation of the anti-apoptotic proteins, MCL-1 and Cflip short.
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DOI：
10.1371/journal.pone.0032971
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Evans DR
中科院分区：
文献类型：
--
作者：
Chen S;Evans HG;Evans DR
FLASH（FLICE相关巨大蛋白或CASP 8AP 2）是一种大型多功能蛋白，参与许多与细胞死亡和存活相关的细胞过程。据报道，它可以促进细胞凋亡，但我们在这里表明，通过siRNA干扰HT 1080细胞中FLASH的消耗也可以加速这一过程。如前所述，FLASH的耗尽通过下调组蛋白生物合成来停止生长，并将细胞周期阻滞在S期。FLASH敲低后用Fas配体或抗Fas抗体刺激细胞，发现与PARP的更快速裂解、caspase-8和刽子手caspase-3的加速活化以及细胞崩解的快速进展相关。与大多数抗凋亡蛋白的情况一样，FLASH在凋亡发生后不久就被降解。FLASH的消耗还导致抗凋亡蛋白MCL-1和cFLIP的短同种型的细胞内水平降低。在p53缺陷的HT 1080突变细胞中的FLASH敲除没有显著加速Fas介导的凋亡，表明该作用依赖于功能性p53。总的来说，这些结果表明，在某些情况下，FLASH抑制细胞凋亡。
FLASH (FLICE-associated huge protein or CASP8AP2) is a large multifunctional protein that is involved in many cellular processes associated with cell death and survival. It has been reported to promote apoptosis, but we show here that depletion of FLASH in HT1080 cells by siRNA interference can also accelerate the process. As shown previously, depletion of FLASH halts growth by down-regulating histone biosynthesis and arrests the cell cycle in S-phase. FLASH knockdown followed by stimulating the cells with Fas ligand or anti-Fas antibodies was found to be associated with a more rapid cleavage of PARP, accelerated activation of caspase-8 and the executioner caspase-3 and rapid progression to cellular disintegration. As is the case for most anti-apoptotic proteins, FLASH was degraded soon after the onset of apoptosis. Depletion of FLASH also resulted in the reduced intracellular levels of the anti-apoptotic proteins, MCL-1 and the short isoform of cFLIP. FLASH knockdown in HT1080 mutant cells defective in p53 did not significantly accelerate Fas mediated apoptosis indicating that the effect was dependent on functional p53. Collectively, these results suggest that under some circumstances, FLASH suppresses apoptosis.
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影响因子：
37.3
作者：
Alm-Kristiansen AH;Lorenzo PI;Molværsmyr AK;Matre V;Ledsaak M;Sæther T;Gabrielsen OS
通讯作者：
Gabrielsen OS
影响因子：
11.4
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64.8
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影响因子：
4.8
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通讯作者：
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影响因子：
4.8
作者：
Kuwana, T;Smith, JJ;Kornbluth, S
通讯作者：
Kornbluth, S