Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unc-51-like kinases (ULKs) are the most upstream kinases in the initiation of autophagy, yet the molecular mechanisms underlying their function are poorly understood. We report a new role for ULK in the induction of autophagy. ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12. Through binding to LC3 and associating with LC3-positive autophagosomes, active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy.
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PMID:Phosphorylation of the exchange factor DENND3 by ULK in response to starvation activates Rab12 and induces autophagy. 2617 9

The small GTP-binding protein Rab12 plays an important role in the initiation of starvation-induced macroautophagy (autophagy) and is activated by the guanine-nucleotide exchange factor DENND3. However, the molecular mechanism by which DENND3 becomes activated has remained elusive. Xu and McPherson now identify a novel mechanism of DENND3 intramolecular binding that is regulated by the phosphorylation of a single tyrosine residue.
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PMID:Into the linker's DENN: A tyrosine's control of autophagy. 2824 39

Autophagy breaks down nonessential cellular components to replenish macromolecular building blocks during starvation. Nevertheless, the downstream events regulating vesicle trafficking during this essential cellular process are not yet fully defined. Xu et al. combined approaches of crystallography, biochemistry, and cell biology to show that the guanine nucleotide exchange factor DENND3 contains an actin-binding site they call "PHenn domain" in a region previously thought to be unstructured. PHenn domain binding to microfilaments is necessary for DENND3's participation in autophagy, providing a new link between autophagic stimulation and actin microfilaments. The findings by Xu et al. shed important new light on how membrane trafficking participates in critical steps of autophagy in relationship with actin microfilaments.
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PMID:A new actin-binding domain glues autophagy together. 2957 27