Results: 2

1.
Figure 2

Figure 2. Dynamic regulation of Beclin 1-VPS34 complex formation and autophagy by Bcl-2 family members and Beclin 1 dimerization. From: Beclin 1-VPS34 complex - At the Crossroads of Autophagy and Beyond.

Beclin 1-VPS34-VPS15 forms pro-autophagic complexes with Atg14L or UVRAG. Binding of Bcl-2 and Beclin 1 is known to inhibit autophagy by possibly disrupting VPS34 binding; but Bcl-2 binding may also displace other stable interacting partners such as Atg14L (or UVRAG), resulting in autophagy inhibition. Additionally, the anti-autophagic binding of Bcl-2 promotes Beclin 1 homodimerization, which prevents heterodimerization with Atg14L or UVRAG.

Sarah F. Funderburk., et al. Trends Cell Biol. 2010 June;20(6):355-362.
2.
Figure 1

Figure 1. Multiple Beclin 1-VPS34 complexes and their distinct functions. From: Beclin 1-VPS34 complex - At the Crossroads of Autophagy and Beyond.

(A) An illustration of the multilayered Beclin 1 protein complexes: a core complex Beclin 1-VPS34-VPS15; stable binding partners Atg14L, UVRAG, and Rubicon; unstable or transient binding partners including Bcl-2 homologs, Bif-1, Ambra 1, VMP1, nPIST, Rab5, ICP 34.5, and inositol 1,4,5-triphosphate receptor (IP3R). Among the unstable binding partners, Bif-1 interacts with UVRAG, and IP3R interacts with Bcl-2.
(B) In yeast two Atg6-Vps34 complexes, I and II, regulate autophagy and vacuolar protein sorting, respectively. In mammals, multiple Beclin 1 complexes act in different stages of autophagy and perhaps also endocytic trafficking. Atg14L associates with the core Beclin 1-VPS34-VPS15 complex to function in the biosynthesis of autophagosomes, and UVRAG potentially associates with the same core complex to also influence autophagosome formation. However, UVRAG has an additional role in autophagosome maturation in a complex with C-Vps and the Rab7 GTPase that is independent of Beclin 1. Rubicon inhibits autophagosome maturation in a possibly Beclin 1-independent manner. Rubicon could sequester Rab proteins such as Rab 7 through its RUN domain to inhibit this stage of autophagy. The binding of Rubicon to the Beclin 1 core complex though UVRAG may aid in neutralizing such a negative function.

Sarah F. Funderburk., et al. Trends Cell Biol. 2010 June;20(6):355-362.

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