Reference: Bueno-Arribas M and Vincent O (2025) Identification of a novel mechanism for regulation of the early autophagy machinery assembly by PKA. Autophagy Rep 4(1):2503226

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Abstract


The E3-like complex Atg12-Atg5-Atg16, which promotes Atg8 lipidation, is recruited to the autophagosomal membrane through the interaction of Atg16 with the PROPPIN/WIPI protein Atg21, as well as by the binding of Atg12 to Atg17, the scaffold protein of the Atg1 kinase complex in yeast. In order to gain insights into the molecular basis of Atg12-Atg17 interaction, we performed reverse two-hybrid screens to identify key-binding residues in both proteins and, based on these data, model the structure of this protein complex. Strikingly, we found that the Atg17 binding site in Atg12 overlaps with a PKA phosphorylation site and that PKA phosphorylation of Atg12 prevents Atg17 binding, revealing a new regulatory mechanism by which PKA regulates the assembly of the autophagy machinery.

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Journal Article
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Bueno-Arribas M, Vincent O
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