Many concurrently published or quickly following arti cles then supplied compelling proof for your existence of a significant autophagy regulating Ulk Atg13 FIP200 com plex, which can be right regulated from the mam malian TOR complicated 1. As stated over, the two Ulk1 and Ulk2 can inter act with Atg13 via their highly conserved C terminal domain, although the interaction concerning Ulk1/2 and FIP200 is primarily mediated via Atg13. In contrast to the yeast Atg1 Atg13 Atg17 complex and in accor dance with all the Drosophila dAtg1 dAtg13 complicated, the composition in the vertebrate Ulk1/2 Atg13 FIP200 complex doesn’t considerably fluctuate in between autophagic and non autophagic circumstances. The phos phorylation standing within the complex, even so, does significantly transform, depending on the current cellular nutrient and energy status.
Beneath optimum development con ditions, the energetic mTORC1 physically interacts together with the Ulk1/2 Atg13 FIP200 complicated and phosphorylates Ulk1/2 and Atg13. mTOR inhibition or nutrient starvation results in a modest decrease in Atg13 and Ulk1 phosphorylation, a cool way to improve and presumably a modest increase in Ulk1/2 kinase action. While the practical relevance has not been established yet, given that the two FIP200 and Atg13 are direct substrates of Ulk1/2, the Ulk1/2 dependent phosphorylation of both proteins may be a trigger for that translocation of Ulk1/2 Atg13 FIP200 to pre autophagosomal structures and for autophagy initiation. Independently, two groups identified a formerly uncharacterized protein as an extra constituent with the vertebrate Ulk1/2 Atg13 FIP200 complex.
This protein is encoded inside the genome of worms A966492 and flies but has no clear homolog in Saccharomyces cere visiae, accordingly it was termed Atg101. It immediately binds and stabilizes Atg13, most likely by stopping its proteasomal degradation. Notably, the closely linked fission yeast species Sac charomyces pombe does possess a putative Atg101 homolog that was originally termed Mug66. Mizushima by now suggested that S. pombe might repre sent an fascinating model system to examine the evolution of autophagic processes for the following rea sons, Like S. cerevisiae it possesses a prospective Atg17 protein plus a putative Atg11 homolog, like greater eukaryotes it lacks Atg29 and Atg31 but rather has an Atg101 homolog. Even so, Taz1IF1 demonstrates a greater similarity to vertebrate FIP200 than to yeast Atg11.
FIP200, alternatively, is assigned as member in the Atg11 household in the NCBI Pfam information base. In addition, yeast Atg17 moreover shows a weak sequence similarity to vertebrate Atg101. In yeast, Atg17 and Atg11 each interact with Atg1 and serve as scaffolding proteins on the PAS, Atg11 underneath standard growth circumstances as part of the cyto plasm to vacuole pathway, Atg17 below nutrient starvation as aspect of the autophagic machinery.
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