在稳态组织中，Mdm2独立于p19(ARF)对p53进行调控。
Mdm2 regulates p53 independently of p19(ARF) in homeostatic tissues.
作者信息
O'Leary Kathleen A, Mendrysa Susan M, Vaccaro Abram, Perry Mary Ellen
机构信息
Department of Oncology, University of Wisconsin, Madison, Wisconsin 53706, USA.
出版信息
Mol Cell Biol. 2004 Jan;24(1):186-91. doi: 10.1128/MCB.24.1.186-191.2004.
Abstract
Tumor suppressor proteins must be exquisitely regulated since they can induce cell death while preventing cancer. For example, the p19(ARF) tumor suppressor (p14(ARF) in humans) appears to stimulate the apoptotic function of the p53 tumor suppressor to prevent lymphomagenesis and carcinogenesis induced by oncogene overexpression. Here we present a genetic approach to defining the role of p19(ARF) in regulating the apoptotic function of p53 in highly proliferating, homeostatic tissues. In contrast to our expectation, p19(ARF) did not activate the apoptotic function of p53 in lymphocytes or epithelial cells. These results demonstrate that the mechanisms that control p53 function during homeostasis differ from those that are critical for tumor suppression. Moreover, the Mdm2/p53/p19(ARF) pathway appears to exist only under very restricted conditions.
摘要
肿瘤抑制蛋白必须受到精确调控，因为它们既能诱导细胞死亡又能预防癌症。例如，p19(ARF)肿瘤抑制蛋白（人类中的p14(ARF)）似乎能刺激p53肿瘤抑制蛋白的凋亡功能，以防止因癌基因过表达诱导的淋巴瘤发生和癌变。在此，我们提出一种遗传学方法，用于确定p19(ARF)在高度增殖的稳态组织中调节p53凋亡功能的作用。与我们的预期相反，p19(ARF)并未激活淋巴细胞或上皮细胞中p53的凋亡功能。这些结果表明，在稳态过程中控制p53功能的机制与对肿瘤抑制至关重要的机制不同。此外，Mdm2/p53/p19(ARF)通路似乎仅在非常有限的条件下存在。
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2
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3
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