کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1928904 1050430 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Caspase-3-mediated cleavage of PICOT in apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Caspase-3-mediated cleavage of PICOT in apoptosis
چکیده انگلیسی

Mammalian protein kinase C-interacting cousin of thioredoxin (PICOT) is a multi-domain mono-thiol glutaredoxin that is involved in several signal transduction pathways and is necessary for cell growth and metastasis. Here, we demonstrate that PICOT is a cleavage substrate of the apoptosis-related protein caspase-3. In vitro cleavage assays indicated that PICOT was specifically cleaved by caspase-3. Similarly, endogenous PICOT was cleaved in cell death responses induced by staurosporine and etoposide. These phenomena were blocked in the presence of a pan-caspase inhibitor. Using site-directed mutagenesis, we identified two putative caspase-3 cleavage sequences in PICOT, DRLD(101)/G and EELD(226)/T. Interestingly, overexpression of either PICOT wild type or the D101A/D226A double point mutant accelerated etoposide-induced activation of caspase-3 whereas siRNA-mediated knockdown of PICOT blocked this phenomenon. Our data raise the possibility that the pro-apoptotic role of PICOT is actively regulated via caspase-3-mediated cleavage.


► PICOT was specifically cleaved by caspase-3.
► PICOT cleavage was found in prototypic caspase-dependent apoptosis.
► Cleavage sequence in PICOT was mapped at DRLD(101) and EELD(226).
► Its proapoptotic role is actively regulated by caspase-3-mediated cleavage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 432, Issue 3, 15 March 2013, Pages 533–538
نویسندگان
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