RT Journal Article
T1 The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
A1 Bueno-Arribas, Miranda
A1 Cruz-Cuevas, Celia
A1 Monforte-Martinez, Beatriz
A1 Navas Hernández, María Ángeles
A1 Escalante, Ricardo
A1 Vincent, Olivier
AB A key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipida-tion. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagosomal structure is mediated by the interaction of Atg16 with the phosphatidylinositol 3-phosphate-binding protein Atg21, and by the association of Atg12 with the scaffold protein of the Atg1 kinase complex, Atg17. Here, we conducted a reverse two-hybrid screen to identify residues in Atg17 and Atg12 critical for Atg17-Atg12 binding, and used these data to generate a docking model of Atg12-Atg5-Atg16 with the Atg17 complex. In this model, a conserved alpha-helix in the N-terminal region of Atg12 binds to the convex side of crescent-shaped Atg17 and appears to form a four-helix bundle with the three helices of Atg17, similar to that described for the binding of Atg31 to Atg17. We further showed that, in agreement with previous work, Atg17-Atg12 and Atg21-Atg16 binding act cooperatively to mediate the recruitment of the E3-like complex, although our results show that alternative mechanisms are involved in this process. Finally, we found that phosphorylation of Atg12 by PKA prevents its interaction with Atg17, thus adding a new reg-ulatory layer in the control of autophagy by the PKA signaling pathway.
PB Elsevier
SN 0022-2836
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/116079
UL https://hdl.handle.net/20.500.14352/116079
LA eng
NO Bueno-Arribas M, Cruz-Cuevas C, Monforte-Martinez B, Navas MA, Escalante R, Vincent O. The PKA signaling pathway regulates the association of the autophagy initiation complex with the lipidation machinery. J Mol Biol. 2025. 437(5):168954.
NO Ministerio de Ciencia, Innovación y Universidades
DS Docta Complutense
RD 8 abr 2025