An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins.
A multiprotein complex composed of Beclin 1, PI(3)KC3 and UVRAG promotes autophagosome formation, while this activity is suppressed by a cohort of antiapoptotic Bcl-2 family members. Recently, we showed that a viral Bcl-2 of murine gamma-herpesvirus 68, known as M11, binds to Beclin 1 with markedly high affinity in comparison with cellular Bcl-2 or Bcl-X(L) that interacts with Beclin 1 weakly.(1) Furthermore, the binding affinity directly correlated with the potency of inhibition of autophagosome formation in cells. Herein, we present additional data showing that Beclin 1 forms a large homo-oligomer, and this oligomerization is partly disrupted by the binding of M11. Oligomerized Beclin 1 is proposed to serve as a platform enabling a concerted action of many molecules of the associating proteins, including Bif-1 that could be directly involved in autophagosome biogenesis on membranes owing to its BAR domain.
Ku
Bonsu
B
Center for Biomolecular Recognition, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
Woo
Jae-Sung
JS
Liang
Chengyu
C
Lee
Kwang-Hoon
KH
Jung
Jae U
JU
Oh
Byung-Ha
BH
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins