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Article Addendum

Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-X_L

Einat Zalckvar, Hanna Berissi, Miriam Eisenstein and Adi Kimchi

Beclin 1, an essential autophagic protein, is a BH3-only protein that binds Bcl-2 anti-apoptotic family members. The dissociation of Beclin 1 from the Bcl-2
inhibitors is essential for its autophagic activity, and therefore is tightly controlled. We recently revealed a novel phosphorylation-based mechanism by which Death
Associated Protein Kinase (DAPk) regulates this process. We found that DAPk phosphorylates Beclin 1 on T119, a critical residue within its BH3 domain, and thus
promotes Beclin 1 dissociation from Bcl-X_L and autophagy induction.¹ Here we report that T119 phosphorylation also reduces the interaction between Beclin 1 and Bcl-2, in
line with the high degree of structural homology between the BH3 binding pockets of Bcl-2 and Bcl-XL proteins. Our results reveal a new phosphorylation-based
mechanism that reduces the interaction of Beclin 1 with its inhibitors to activate the autophagic machinery.

Addendum to: Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M, Sabanay H, Pinkas-Kramarski R, Kimchi A. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO reports 2009; 10:285-92; PMID: 19180116; DOI: 10.1038/embor.2008.246.

Authors

Einat Zalckvar

Department of Molecular Genetics; Weizmann Institute of Science; Rehovot, Israel

Hanna Berissi

Department of Molecular Genetics; Weizmann Institute of Science; Rehovot, Israel

Miriam Eisenstein

Chemical Research Support; Weizmann Institute of Science; Rehovot, Israel

Adi Kimchi Corresponding author: Adi.Kimchi@weizmann.ac.il

Department of Molecular Genetics; Weizmann Institute of Science; Rehovot, Israel