کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2048961 1074107 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Counteracting MDM2-induced HIPK2 downregulation restores HIPK2/p53 apoptotic signaling in cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Counteracting MDM2-induced HIPK2 downregulation restores HIPK2/p53 apoptotic signaling in cancer cells
چکیده انگلیسی

Homeodomain-interacting protein kinase-2 (HIPK2) is a crucial regulator of p53 apoptotic function by phosphorylating serine 46 (Ser46) in response to DNA damage. In tumors with wild-type p53, its tumor suppressor function is often impaired by MDM2 overexpression that targets p53 for proteasomal degradation. Likewise, MDM2 targets HIPK2 for protein degradation impairing p53-apoptotic function. Here we report that zinc antagonised MDM2-induced HIPK2 degradation as well as p53 ubiquitination. The zinc inhibitory effect on MDM2 activity leads to HIPK2-induced p53Ser46 phosphorylation and p53 pro-apoptotic transcriptional activity. These results suggest that zinc derivatives are potential molecules to target the MDM2-induced HIPK2/p53 inhibition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 584, Issue 19, 8 October 2010, Pages 4253–4258
نویسندگان
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