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Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase
Published on: June 30, 2023
Atg14: a key player in orchestrating autophagy
Keisuke Obara1, Yoshinori Ohsumi
1Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Jo Nishi-6 Chome, Kitaku, Sapporo 060-0812, Japan.
Abstract:
Phosphorylation of phosphatidylinositol (PtdIns) by a PtdIns 3-kinase is an essential process in autophagy. Atg14, a specific subunit of one of the PtdIns 3-kinase complexes, targets the complex to the probable site of autophagosome formation, thereby, sorting the complex to function specifically in autophagy. The N-terminal half of Atg14, containing coiled-coil domains, is required to form the PtdIns 3-kinase complex and target it to the proper site. The C-terminal half of yeast Atg14 is suggested to be involved in the formation of a normal-sized autophagosome. The C-terminal half of mammalian Atg14 contains the Barkor/Atg14(L) autophagosome-targeting sequence (BATS) domain that preferentially binds to the highly curved membranes containing PtdIns(3)P and is proposed to target the PtdIns 3-kinase complex efficiently to the isolation membrane. Thus, the N- and C-terminal halves of Atg14 are likely to have an essential core function and a regulatory role, respectively.
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