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 language | English (US) |
---|---|
Title of host publication | Autophagy |
Subtitle of host publication | Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 8- Human Diseases |
Publisher | Elsevier |
Pages | 75-88 |
Number of pages | 14 |
ISBN (Electronic) | 9780128029374 |
ISBN (Print) | 9780128029527 |
DOIs | |
State | Published - Jan 1 2016 |
Externally published | Yes |
Keywords
- BCL-2
- Beclin 1
- Beclin 1-BCL-2 complex
- Beclin 1-PI3KC3 core complex
- PI3KC3
- apoptosis
- autophagy
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology