کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151395 | 1089988 | 2013 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Removal of the BH4 Domain from Bcl-2 Protein Triggers an Autophagic Process that Impairs Tumor Growth
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کلمات کلیدی
eGFPBcl-2PARPAVOsLC3BCDDPAcidic vesicular organelles - اندام های حسی اسیدیBrdU - بروموداکسی اوریدینbromodeoxyuridine - برومودسوویریدینcisplatin - سیس پلاتینIntramuscular - عضلانیB-cell lymphoma 2 - لنفوم سلول B 2i.m. - من هستم.short hairpin - موی سر کوتاهwild type - نوع وحشیBcl-2 homology - همولوگ Bcl-2enhanced green fluorescent protein - پروتئین فلورسنت سبز افزایش یافته استPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2) protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4) domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1) the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2) Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3) BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 15, Issue 3, March 2013, Pages 315-327, IN36-IN37
Journal: Neoplasia - Volume 15, Issue 3, March 2013, Pages 315-327, IN36-IN37
نویسندگان
Daniela Trisciuoglio, Teresa De Luca, Marianna Desideri, Daniela Passeri, Chiara Gabellini, Stefania Scarpino, Chengyu Liang, Augusto Orlandi, Donatella Del Bufalo,