کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1984338 1539973 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MDM2 and MDM4: p53 regulators as targets in anticancer therapy
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
MDM2 and MDM4: p53 regulators as targets in anticancer therapy
چکیده انگلیسی

The gene TP53, encoding transcription factor p53, is mutated or deleted in half of human cancers, demonstrating the crucial role of p53 in tumor suppression. Importantly, p53 inactivation in cancers can also result from the amplification/overexpression of its specific inhibitors MDM2 and MDM4 (also known as MDMX). The presence of wild-type p53 in those tumors with MDM2 or MDM4 overexpression stimulates the search for new therapeutic agents to selectively reactivate it. This short survey highlights recent insights into MDM2 and MDM4 regulatory functions and their implications for the design of future p53-based anticancer strategies. We now know that MDM2 and MDM4 inhibit p53 in distinct and complementary ways: MDM4 regulates p53 activity, while MDM2 mainly regulates p53 stability. Upon DNA damage, MDM2-dependent degradation of itself and MDM4 contribute significantly to p53 stabilization and activation. These and other data imply that the combined use of MDM2 and MDM4 antagonists in cancer cells expressing wild-type p53 should activate p53 more significantly than agents that only antagonize MDM2, resulting in more effective anti-tumor activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 39, Issues 7–8, July–August 2007, Pages 1476–1482
نویسندگان
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