DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy

Einat Zalckvar, Hanna Berissi, Liat Mizrachy, Yulia Idelchuk, Itay Koren, Miriam Eisenstein, Helena Sabanay, Ronit Pinkas-Kramarski, Adi Kimchi

Research output: Contribution to journalArticlepeer-review

Abstract

Autophagy, an evolutionarily conserved process, has functions both in cytoprotective and programmed cell death mechanisms. Beclin 1, an essential autophagic protein, was recently identified as a BH3-domain-only protein that binds to Bcl-2 anti-apoptotic family members. The dissociation of beclin 1 from its Bcl-2 inhibitors is essential for its autophagic activity, and therefore should be tightly controlled. Here, we show that death-associated protein kinase (DAPK) regulates this process. The activated form of DAPK triggers autophagy in a beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl-XL and the induction of autophagy. These results reveal a substrate for DAPK that acts as one of the core proteins of the autophagic machinery, and they provide a new phosphorylation-based mechanism that reduces the interaction of beclin 1 with its inhibitors to activate the autophagic machinery.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalEMBO Reports
Volume10
Issue number3
DOIs
StatePublished - 2009

Fingerprint

Dive into the research topics of 'DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy'. Together they form a unique fingerprint.

Cite this