کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2130644 1086589 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Parkin Co-Regulated Gene is involved in aggresome formation and autophagy in response to proteasomal impairment
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Parkin Co-Regulated Gene is involved in aggresome formation and autophagy in response to proteasomal impairment
چکیده انگلیسی

PArkin Co-Regulated Gene is a gene that shares a bidirectional promoter with the Parkinson's disease associated gene parkin. The encoded protein (PACRG) is found in Lewy bodies and glial cytoplasmic inclusions, the pathological hallmarks of parkinsonian disorders. To investigate the function and regulation of PACRG, cells were treated with the proteasomal inhibitor, MG-132. As previously reported with parkin, inhibition of the proteasome resulted in the formation of aggresomes that contained endogenous PACRG. Increased levels of exogenous PACRG resulted in an increase in aggresome formation, and conferred significant resistance to aggresome disruption and cell death mediated by microtubule depolymerisation. In contrast, shRNA mediated knockdown of PACRG significantly reduced aggresome numbers. Elevated levels of PACRG also resulted in increased autophagy, as demonstrated by biochemical and quantitative analysis of autophagic vesicles, whereas lowered levels of PACRG resulted in reduced autophagy. These results suggest a role for PACRG in aggresome formation and establish a further link between the UPS and autophagy.


► PACRG is a component of aggresomes induced by proteasome inhibition.
► PACRG expression is associated with microtubule‐resistant aggresomes.
► Reduced levels of PACRG were associated with decreased autophagy.
► PACRG is a mediator of the UPS and autophagy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 318, Issue 16, 1 October 2012, Pages 2059–2070
نویسندگان
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