کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10901358 | 1084694 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RNF12 promotes p53-dependent cell growth suppression and apoptosis by targeting MDM2 for destruction
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The oncoprotein MDM2 is an E3 ubiquitin ligase that targets tumor suppressor p53 for ubiquitination and proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. Dysregulation of MDM2-p53 axis was frequently observed in human cancers. Originally, it is proposed that MDM2 degradation was mainly achieved by destructive self-ubiquitination. However, recent study suggests that MDM2 may be targeted for degradation by an external E3 ubiquitin ligase(s) under physiological levels. Here, we identified E3 ubiquitin ligase RNF12 as an MDM2-interacting protein through yeast two hybrid methods. We demonstrated that RNF12 targets MDM2 for ubiquitination and proteasomal-dependent degradation, which is independent of MDM2's self-ubiquitination activity. Accordingly, RNF12 elevates p53 protein level by abrogating MDM2-mediated p53 degradation and ubiquitination. Finally, we showed that RNF12 regulates cell growth suppression and DNA damage-induced apoptosis in a p53-dependent manner. Taken together, we establish RNF12 as a novel positive regulator of p53 pathway and an external E3 ubiquitin ligase for MDM2 destruction. These data shed light on the potential roles of RNF12 in MDM2-p53 axis and tumor suppression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 375, Issue 1, 28 May 2016, Pages 133-141
Journal: Cancer Letters - Volume 375, Issue 1, 28 May 2016, Pages 133-141
نویسندگان
Kun Gao, Chenji Wang, Xiaofeng Jin, Jiantao Xiao, Enceng Zhang, Xianmei Yang, Dejie Wang, Haojie Huang, Long Yu, Pingzhao Zhang,