视网膜母细胞瘤抑癌蛋白的促凋亡功能。
Proapoptotic function of the retinoblastoma tumor suppressor protein.
作者信息
Ianari Alessandra, Natale Tiziana, Calo Eliezer, Ferretti Elisabetta, Alesse Edoardo, Screpanti Isabella, Haigis Kevin, Gulino Alberto, Lees Jacqueline A
机构信息
David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
出版信息
Cancer Cell. 2009 Mar 3;15(3):184-94. doi: 10.1016/j.ccr.2009.01.026.
Abstract
The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell-cycle genes. E2F1 can also activate proapoptotic genes in response to genotoxic or oncogenic stress. However, pRB's role in this context has not been established. Here we show that DNA damage and E1A-induced oncogenic stress promote formation of a pRB-E2F1 complex even in proliferating cells. Moreover, pRB is bound to proapoptotic promoters that are transcriptionally active, and pRB is required for maximal apoptotic response in vitro and in vivo. Together, these data reveal a direct role for pRB in the induction of apoptosis in response to genotoxic or oncogenic stress.
摘要
视网膜母细胞瘤蛋白（pRB）肿瘤抑制因子通过抑制E2F转录因子来阻断细胞增殖。这种抑制作用通过有丝分裂原诱导的pRB磷酸化得以解除，从而触发E2F释放并激活细胞周期基因。E2F1也可响应基因毒性或致癌应激激活促凋亡基因。然而，pRB在此背景下的作用尚未明确。在此我们表明，即使在增殖细胞中，DNA损伤和E1A诱导的致癌应激也会促进pRB-E2F1复合物的形成。此外，pRB与转录活跃的促凋亡启动子结合，并且在体外和体内，最大程度的凋亡反应都需要pRB。这些数据共同揭示了pRB在响应基因毒性或致癌应激诱导细胞凋亡中的直接作用。
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本文引用的文献
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Retinoblastoma function is essential for establishing lung epithelial quiescence after injury.视网膜母细胞瘤功能对于损伤后建立肺上皮静止状态至关重要。
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Life and death decisions by the E2F transcription factors.E2F转录因子对生死的调控作用
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The retinoblastoma protein, RB, is required for gastrointestinal endocrine cells to exit the cell cycle, but not for hormone expression.视网膜母细胞瘤蛋白RB是胃肠道内分泌细胞退出细胞周期所必需的，但对于激素表达并非必需。
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E2f4 is required for normal development of the airway epithelium.E2f4是气道上皮正常发育所必需的。
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Inactivation of conditional Rb by Villin-Cre leads to aggressive tumors outside the gastrointestinal tract.通过绒毛蛋白-cre使条件性Rb失活会导致胃肠道外出现侵袭性肿瘤。
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The related retinoblastoma (pRb) and p130 proteins cooperate to regulate homeostasis in the intestinal epithelium.相关的视网膜母细胞瘤（pRb）蛋白和p130蛋白协同调节肠上皮细胞的稳态。
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