Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-X<sub>L</sub>

Zalckvar, Einat; Berissi, Hanna; Eisenstein, Miriam; Kimchi, Adi

doi:10.4161/auto.5.5.8625

Cited by 226 publications

(189 citation statements)

References 12 publications

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“…For example, several BH3-only proteins, such as Bcl-2-associated death promoter protein (Bad), tBid (truncated BH3 interacting domain death agonist) and BNIP3, abrogate the Bcl-2-Beclin-1 interaction by competing with Beclin-1 for Bcl-2 binding. Furthermore, other apoptotic modulators (death-associated protein kinase, c-jun N-terminal kinase, TRAF6 and A20) mediate Beclin-1 or Bcl-2 post-translational modifications that enable dissociation of Beclin-1 from Bcl-2 [103,142,143]. Surprisingly, caspases were also implicated in autophagy-mediated survival.…”

Section: Atg12-atg3mentioning

confidence: 99%

Autophagy: for better or for worse

et al. 2011

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Autophagy is a lysosomal degradation pathway that degrades damaged or superfluous cell components into basic biomolecules, which are then recycled back into the cytosol. In this respect, autophagy drives a flow of biomolecules in a continuous degradation-regeneration cycle. Autophagy is generally considered a pro-survival mechanism protecting cells under stress or poor nutrient conditions. Current research clearly shows that autophagy fulfills numerous functions in vital biological processes. It is implicated in development, differentiation, innate and adaptive immunity, ageing and cell death. In addition, accumulating evidence demonstrates interesting links between autophagy and several human diseases and tumor development. Therefore, autophagy seems to be an important player in the life and death of cells and organisms. Despite the mounting knowledge about autophagy, the mechanisms through which the autophagic machinery regulates these diverse processes are not entirely understood. In this review, we give a comprehensive overview of the autophagic signaling pathway, its role in general cellular processes and its connection to cell death. In addition, we present a brief overview of the possible contribution of defective autophagic signaling to disease.

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Section: Atg12-atg3mentioning

confidence: 99%

Autophagy: for better or for worse

et al. 2011

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“…The interaction of Beclin 1 with its binding partners has been shown to be regulated by the phosphorylation of Beclin 1 by various Ser/Thr kinases. For instance, death-associated protein kinase 1 (DAPK1) phosphorylates Thr-119 of Beclin 1, which leads to the dissociation of Bcl-2 and Bcl-xL from Beclin 1 and promotes autophagy (8,9). Conversely, Akt/PKB-mediated phosphorylation of Ser-234 and Ser-295 of Beclin 1 inhibits autophagy (10).…”

mentioning

confidence: 99%

Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3)

Fujiwara¹,

Usui

Ohama³

et al. 2016

Journal of Biological Chemistry

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Autophagy is an evolutionarily conserved intracellular degradation system that is involved in cell survival and activated in various diseases, including cancer. Beclin 1 is a central scaffold protein that assembles components for promoting or inhibiting autophagy. Association of Beclin 1 with its interacting proteins is regulated by the phosphorylation of Beclin 1 by various Ser/ Thr kinases, but the Ser/Thr phosphatases that regulate these phosphorylation events remain unknown. Here we identify Ser-90 in Beclin 1 as a regulatory site whose phosphorylation is markedly enhanced in cells treated with okadaic acid, an inhibitor of protein phosphatase 2A (PP2A). Beclin 1 Ser-90 phosphorylation is induced in skeletal muscle tissues isolated from starved mice. The Beclin 1 S90A mutant blocked starvationinduced autophagy. We found association of PP2A B55␣ with Beclin 1, which dissociate by starvation. We also found that death-associated protein kinase 3 directly phosphorylates Beclin 1 Ser-90. We propose that physiological regulation of Beclin 1 Ser-90 phosphorylation by PP2A and death-associated protein kinase 3 controls autophagy.

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“…In its capacity as a transcriptional repressor, DAXX associates with RelB, a transcription factor of the NF-B family that directly controls the expression of the DAPK1/3 tumor suppressor protein kinases (2), which are linked to autophagy (4,5). Through its ability to repress tumor suppressors and autophagy regulators via a mechanism involving association with RelB and subsequent target promoter DNA methylation (2), DAXX would be expected to induce tumor growth or survival.…”

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confidence: 99%

Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy

Puto

Brognard

Hunter

2015

Journal of Biological Chemistry

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Background: Transcriptional repressor DAXX suppresses several tumor suppressor genes and is up-regulated in many cancers. Results: We demonstrate that DAXX has potent growth-enhancing effects on primary prostatic malignancy through inhibition of autophagy. Conclusion: In the early stages of tumorigenesis, autophagy suppresses prostate tumor formation. Significance: This is the first study to link prostate cancer development to autophagy suppression by DAXX.

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

Cited by 226 publications

References 12 publications

Autophagy: for better or for worse

Autophagy: for better or for worse

Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3)

Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy

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

Cited by 226 publications

References 12 publications

Autophagy: for better or for worse

Autophagy: for better or for worse

Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3)

Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy

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