کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5934318 | 1573405 | 2013 | 11 صفحه PDF | دانلود رایگان |
S-phase kinase-associated protein 2 (Skp2) functions as the receptor component of the Skp-Cullin-F-box complex and is implicated in the degradation of several cell cycle regulators, such as p21Cip1, p27Kip1, p57Kip2, and cyclin E. Numerous studies in human and experimental tumors have demonstrated low p27Kip1 levels and elevated Skp2 expression. However, a direct association between the inverse correlation of Skp2 and p27Kip1 with tumorigenesis has not been demonstrated. Herein, we provide evidence that skin tumorigenesis is inhibited in Skp2â/â mice. An analysis of mouse keratinocytes indicates that increased p27Kip1 levels in Skp2â/â epidermis cause reduced cell proliferation that is alleviated in the epidermis from Skp2â/â/p27â/â compound mice. In contrast, we establish that a p27Kip1 deficiency does not overturn the reduced skin tumorigenesis experienced by Skp2â/â mice. In addition, Skp2â/â epidermis exhibits an accumulation of p53-cofactor CBP/p300 that is associated with elevated apoptosis in hair follicles and decreased skin tumorigenesis. We conclude that p27Kip1 accumulation is responsible for the hypoplasia observed in normal tissues of Skp2â/â mice but does not have a preponderant function in reducing skin tumorigenesis.
Journal: The American Journal of Pathology - Volume 182, Issue 5, May 2013, Pages 1854-1864