An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins

Bonsu Ku; Jae Sung Woo; Chengyu Liang; Kwang Hoon Lee; Jae U. Jung; Byung Ha Oh

doi:10.4161/auto.5846

An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins

Bonsu Ku, Jae Sung Woo, Chengyu Liang, Kwang Hoon Lee, Jae U. Jung, Byung Ha Oh

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

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 γ-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.

Original language	English
Pages (from-to)	519-520
Number of pages	2
Journal	Autophagy
Volume	4
Issue number	4
DOIs	https://doi.org/10.4161/auto.5846
Publication status	Published - 2008 May 16
Externally published	Yes

Keywords

Autophagy
Bcl-2
Beclin 1
M11
Oligomerization

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.4161/auto.5846

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title = "An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins",

abstract = "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 γ-herpesvirus 68, known as M11, binds to Beclin 1 with markedly high affinity in comparison with cellular Bcl-2 or Bcl-XL 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.",

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AU - Ku, Bonsu

AU - Woo, Jae Sung

AU - Liang, Chengyu

AU - Lee, Kwang Hoon

AU - Jung, Jae U.

AU - Oh, Byung Ha

PY - 2008/5/16

Y1 - 2008/5/16

N2 - 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 γ-herpesvirus 68, known as M11, binds to Beclin 1 with markedly high affinity in comparison with cellular Bcl-2 or Bcl-XL 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.

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An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins

Abstract

Keywords

ASJC Scopus subject areas

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