Bcl-2 family members: Dual regulators of apoptosis and autophagy

By Beth Levine, Sangita C. Sinha, Guido Kroemer. Autophagy, 2008

752 citations recorded by the source corpus.

The essential autophagy protein and haplo-insufficient tumor suppressor, Beclin 1, interacts with several cofactors (Ambra1, Bif-1, UVRAG) to activate the lipid kinase Vps34, thereby inducing autophagy. In normal conditions, Beclin 1 is bound to and inhibited by Bcl-2 or the Bcl-2 homolog Bcl-XL. This interaction involves a Bcl-2 homology 3 (BH3) domain in Beclin 1 and the BH3 binding groove of Bcl-2/Bcl-XL. Other proteins containing BH3 domains, called BH3-only proteins, can competitively disrupt the interaction between Beclin 1 and Bcl-2/Bcl-XL to induce autophagy. Nutrient starvation, which is a potent physiologic inducer of autophagy, can stimulate the dissociation of Beclin 1 from its inhibitors, either by activating BH3-only proteins (such as Bad) or by posttranslational modifications of Bcl-2 (such as phosphorylation) that may reduce its affinity for Beclin 1 and BH3-only proteins. Thus, anti-apoptotic Bcl-2 family members and pro-apoptotic BH3-only proteins may participate in the inhibition and induction of autophagy, respectively. This hitherto neglected crosstalk between the core machineries regulating autophagy and apoptosis may redefine the role of Bcl-2 family proteins in oncogenesis and tumor progression.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/079ad87fc61ec77dff5f3754a564dbeff0a24ba7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. Yongqiang Chen
2. D. Klionsky
3. J. Chiche
4. J. Pouysségur
5. N. Mizushima
6. G. Hotamışlıgil
7. Beth Levine
8. I. Slaninová

In Epidemiology

1. Yongqiang Chen
2. D. Klionsky
3. G. Semenza
4. I. Slaninová
5. Guido Kroemer
6. Beth Levine
7. N. Mizushima
8. Katherine R Parzych

In Molecular Biology

1. J. Chiche
2. J. Pouysségur
3. Yongqiang Chen
4. N. Mazure
5. G. Semenza
6. D. Klionsky
7. I. Slaninová
8. Guido Kroemer

Citations in the corpus

• Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains (2009, background): “recently suggested that Beclin1 acts as an interactome in the regulation of apoptosis rather than autophagy (15).”
• The Role of Autophagy in Cancer: Therapeutic Implications (2011, background): “indicate that they can also inhibit autophagy (78).”
• The regulation of autophagy – unanswered questions (2011, background): “Proteins such as UVRAG, AMBRA1, Atg14L, and Bif-1 positively regulate autophagy, whereas other class III PtdIns3K-interacting proteins such as rubicon, Bcl-2 and Bcl-xL are negative regulators.”