Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
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DOI：
10.1073/pnas.2436255100
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发表时间：
2003-12-09
影响因子：
11.1
通讯作者：
Heintz, N
中科院分区：
文献类型：
--
作者：
Yue, ZY;Jin, SK;Heintz, N
beclin 1的生化特性表明其在两个基本重要的细胞生物学途径中发挥作用：自噬和凋亡。我们发现，beclin 1（-/-）突变小鼠在胚胎发育早期死亡，而beclin 1（+/-）突变小鼠自发性肿瘤的发生率很高。这些肿瘤继续表达野生型beclin 1 mRNA和蛋白，从而确定beclin 1是一种单倍不足的肿瘤抑制基因。Beclin 1（-/-）胚胎干细胞具有严重改变的自噬反应，而它们对血清撤回或UV光的凋亡反应是正常的。这些结果表明，beclin 1是哺乳动物自噬的关键组分，并确立了自噬在肿瘤抑制中的作用。他们都为最近的证据提供了生物学解释，这些证据表明beclin 1与人类癌症有关，并表明在这一途径中起作用的其他基因的突变可能通过自噬的失调而导致肿瘤的形成。
The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1(-/-) mutant mice die early in embryogenesis and beclin 1(+/-) mutant mice suffer from a high incidence of spontaneous tumors. These tumors continue to express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a haploinsufficient tumor suppressor gene. Beclin 1(-/-) embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal. These results demonstrate that beclin 1 is a critical component of mammalian autophagy and establish a role for autophagy in tumor suppression. They both provide a biological explanation for recent evidence implicating beclin 1 in human cancer and suggest that mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of autophagy.