کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1940673 | 1050786 | 2006 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mdm2-mediated pRB downregulation is involved in carcinogenesis in a p53-independent manner
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mdm2 promotes ubiquitination of the tumor suppressor p53 and can function as an oncogene by largely downregulating p53. Although a p53-independent role of Mdm2 has been reported, the underlying mechanism remains unclear. In the present study, we indicated that Mdm2 is involved in p53-independent carcinogenesis via downregulation of pRB. Expression of pRB showed an apparent inverse correlation with Mdm2 expression in 30 patients with non-small cell lung cancer. There were some cases with the p53 mutations in which a high level of Mdm2 and a low level of pRB were expressed. Mdm2 promoted ubiquitination of pRB in cells without wild-type p53. Furthermore, pRB-mediated G1 arrest in a p53-deficient cell line, SRB1, was significantly enhanced by a mutant Mdm2 that lacks pRB ubiquitination activity. Soft-agar colony formation activity of p53-knockout MEF was increased by wild-type Mdm2 but not mutant Mdm2. These findings suggest that overexpression of Mdm2 can perturb a RB pathway regardless of the p53 gene status, promoting carcinogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 340, Issue 1, 3 February 2006, Pages 54-61
Journal: Biochemical and Biophysical Research Communications - Volume 340, Issue 1, 3 February 2006, Pages 54-61
نویسندگان
Seiichi Miwa, Chiharu Uchida, Kyoko Kitagawa, Takayuki Hattori, Toshiaki Oda, Haruhiko Sugimura, Hideyo Yasuda, Hirotoshi Nakamura, Kingo Chida, Masatoshi Kitagawa,