Common and divergent functions of Beclin 1 and Beclin 2
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摘要:
Originally identified as a BCL-2-interacting partner capable of protecting mice from viral encephalitis [1],Beclin 1-the mammalian ortholog of yeast Atg6-is nowadays well known as a core component of the class Ⅲ phosphoinosite-3-kinase (PI3K) enzymatic complex that initiates the formation of autophagosomes in the course of macroautophagy (hereafter referred to as autophagy) [2].Presumably owing to the critical function of autophagy in embryonic development,mice lacking both copies of the Beclin 1-coding gene (Becn1) die early during embryogenesis.Moreover,Becn1+/-mice suffer from a high incidence of spontaneous tumors,indicating that Beclin 1 acts as a haploinsufficient tumor suppressor [3].At least in part,this reflects the central role that autophagy plays in the maintenance of intracellular homeostasis.Indeed,baseline levels of autophagy mediate the removal of various cytoplasmic entities that might favor oncogenesis,including damaged mitochondria and protein aggregates [4].Conversely,established neoplasms often harness the cytoprotective functions of autophagy to their own benefit [2].The pathophysiological relevance of autophagy is not limited to cancer,but extends to a large panel of human diseases,including neurodegenerative,cardiovascular and infectious conditions [5].Thus,during the last decade autophagy-regulatory signaling pathways have been intensively investigated.