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Y. Zhang, Y. Xiong and W. G. Yarbrough, “ARF Promotes MDM2 Degradation and Stabilizes p53: ARFINK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways,” Cell, Vol. 92, No. 6, 1998, pp. 725-734. doi:10.1016/S0092-8674(00)81401-4

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• TITLE: REGγ Mediated Regulation of p21Waf/Cip1, p16INK4a and p14ARF/p19ARF in Vivo

  AUTHORS: Lei Li, Pei Zhang, Haibin Wei, Weicang Wang, Liangfang Yao, Yubing Li, Lei Zhou, Zhuo Wang, Jiang Liu, Li Zhou, Ali Amjad, Bianhong Zhang, Tiantian Jing, Jianru Xiao, Yongyan Dang, Xiaotao Li

  KEYWORDS: REGγ; p21Waf/Cip1;p16INK4a; p14ARF; p19ARF; Cancer

  JOURNAL NAME: Journal of Cancer Therapy, Vol.4 No.5, June 28, 2013

  ABSTRACT: p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-degradation of p21Waf/Cip1, p16INK4a and p14ARF remain unclear. In this study, we showed enhanced expression of p21Waf/Cip1, p16INK4a and p19ARF in multiple tissues from REGg–/– mice compared to REGg+/+ mice. Furthermore, we examined the expression of p21Waf/Cip1, p16INK4a and p14ARF in different cancer tissues and observed that the REGγ protein levels were highly expressed in different human cancers while the level of p21Waf/Cip1, p16INK4a and p14ARF appears to be inversely correlated. These results demonstrate that REGγ may exert its function in physiological and pathological conditions through degradation of p21Waf/Cip1, p16INK4a and p14ARF in vivo.