TY - JOUR
T1 - The Beclin 1 network regulates autophagy and apoptosis
AU - Kang, R.
AU - Zeh, H. J.
AU - Lotze, M. T.
AU - Tang, D.
N1 - Funding Information:
Acknowledgements. We thank the numerous colleagues in the field of autophagy, who through their animated discussions have helped shape this review. We would particularly like to thank Dr. Beth Levine who generously critiqued the article and improved it based on her insights and pioneering work in the area of Beclin 1 biology. We also thank Christine Heiner for careful editing of the paper. The development of a metabolism and mitochondria in disease working group with Dr. Bennett Van Houten, who has provided reflection and encouragement for our studies is appreciated. Work in our laboratory is generously supported by the University of Pittsburgh Department of Surgery (Dr. Timothy Billiar), the University of Pittsburgh Cancer Institute (Dr. Nancy Davidson) and the National Institutes of Health via a grant from the National Cancer Institute (P01 CA 101944-04 to Michael T Lotze, MD).
PY - 2011/4
Y1 - 2011/4
N2 - Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP3R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy.
AB - Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP3R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy.
KW - Bcl-2
KW - Beclin 1
KW - PI3K
KW - apoptosis
KW - autophagy
KW - signal transduction
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U2 - 10.1038/cdd.2010.191
DO - 10.1038/cdd.2010.191
M3 - Review article
C2 - 21311563
AN - SCOPUS:79952628267
SN - 1350-9047
VL - 18
SP - 571
EP - 580
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 4
ER -