کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2107825 | 1083703 | 2008 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Mitochondrial p32 Is a Critical Mediator of ARF-Induced Apoptosis Mitochondrial p32 Is a Critical Mediator of ARF-Induced Apoptosis](/preview/png/2107825.png)
SummaryThe shared exon 2 of the p14ARF-p16INK4a locus is frequently mutated in human cancers. However, in contrast to the exon 1β-encoded N-terminal half of ARF, the function of the exon 2-encoded C-terminal half of ARF has been elusive. Here, we report that the mitochondrial protein p32/C1QBP binds the ARF C terminus. We show that p32 is required for ARF to localize to mitochondria and induce apoptosis, and that ARF mutations specifically disrupting p32 binding can impair both of these functions. Wild-type ARF, but not a p32-binding-deficient ARF mutant, localizes to mitochondria, reduces mitochondrial membrane potential, and sensitizes cells to p53-induced apoptosis. These findings provide a potential explanation for the frequent human cancer mutations targeting the ARF C terminus.
Journal: - Volume 13, Issue 6, 10 June 2008, Pages 542–553