Role of the Beclin 1 Network in the Cross-Regulation Between Autophagy and Apoptosis

Yangchun Xie, Rui Kang, Daolin Tang

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Beclin 1, the mammalian homologue of yeast Atg6, is the subunit of class III phosphatidylinositol 3-kinase (PI3KC3, also termed Vps34 in yeast) complex, which plays a critical role in controlling the mammalian autophagic process in response to physiological and pathological stress. The activity of Beclin 1 in this process is regulated by several factors such as transcriptional control, posttranslational modifications, and protein–protein interactions. The binding of Beclin 1 to positive cofactors (e.g., ATG14, NRBF2, UVRAG, BIF-1, RUBICON, AMBRA1, HMGB1, PINK1, and PARKIN) promotes the formation of Beclin 1-PI3KC3 core complex in the initiation of autophagosome formation in autophagy. In contrast, the binding of Beclin 1 to negative cofactors (e.g., BCL-2 or BCL-XL) prevents the formation of the Beclin 1-PI3KC3 core complex in autophagy. Importantly, Beclin 1-mediated autophagy generally limits apoptosis by inhibiting effector caspase degradation, whereas caspase-mediated cleavage of Beclin 1 in apoptosis prevents against autophagy. Thus, the Beclin 1 network plays a central role in the cross-regulation between autophagy and apoptosis. This chapter focuses on the structure and function of Beclin 1 as an important regulator of autophagy, as well as its role in apoptosis.

Original languageEnglish (US)
Title of host publicationAutophagy
Subtitle of host publicationCancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 8- Human Diseases
PublisherElsevier
Pages75-88
Number of pages14
ISBN (Electronic)9780128029374
ISBN (Print)9780128029527
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • apoptosis
  • autophagy
  • BCL-2
  • Beclin 1
  • Beclin 1-BCL-2 complex
  • Beclin 1-PI3KC3 core complex
  • PI3KC3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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