Wang Jianrong
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Autophagy. 2008 Oct;4(7):947-8. doi: 10.4161/auto.6787. Epub 2008 Oct 14.
Beclin 1 is a critical component in the class III PI3 kinase complex (PI3KC3) that induces the formation of autophagosomes in mammalian systems. Autophagic triggers upregulate Beclin 1, which in turn binds to PI3KC3 or Bcl-X(L) to form complexes of Beclin 1-PI3KC3 or Beclin 1-Bcl-X(L) that are physically and functionally independent from each other. Contrary to the previous observations that Beclin 1 binding to Bcl-2 family members is apoptotic and antiautophagic, we found that autophagic trigger-induced Beclin 1-binding to Bcl-X(L) is antiapoptotic and has no effect on autophagy, suggesting a convertible role of the Beclin 1-Bcl-X(L) complex in response to autophagy stimuli. Both autophagy and differentiation cascades require upregulation of Beclin 1. While the basal Beclin 1 level does not cause autophagy or differentiation, depletion of Beclin 1 cripples both autophagy and differentiation capabilities, but activates apoptosis. These results demonstrate that Beclin 1 is essential for autophagy, differentiation and antiapoptosis, and may play an important role in coordinating inputs for cellular decisions to signaling machinery that mediates different cellular cascades.
Beclin 1是III类磷脂酰肌醇3激酶复合物（PI3KC3）中的关键成分，该复合物可诱导哺乳动物系统中自噬体的形成。自噬触发因素上调Beclin 1，Beclin 1继而与PI3KC3或Bcl-X(L)结合，形成Beclin 1-PI3KC3或Beclin 1-Bcl-X(L)复合物，它们在物理和功能上相互独立。与之前关于Beclin 1与Bcl-2家族成员结合具有凋亡和抗自噬作用的观察结果相反，我们发现自噬触发因素诱导的Beclin 1与Bcl-X(L)的结合具有抗凋亡作用，且对自噬无影响，这表明Beclin 1-Bcl-X(L)复合物在响应自噬刺激时具有可转换的作用。自噬和分化级联反应都需要上调Beclin 1。虽然基础水平的Beclin 1不会引起自噬或分化，但Beclin 1的缺失会削弱自噬和分化能力，但会激活凋亡。这些结果表明，Beclin 1对自噬、分化和抗凋亡至关重要，并且可能在协调细胞决策输入与介导不同细胞级联反应的信号传导机制中发挥重要作用。
