title: Tap42-associated protein phosphatase type 2A negatively regulates induction of autophagy.
abstract: Autophagy is a highly conserved degradative process in eukaryotic cells. This process plays an integral role in cellular physiology, and the levels of autophagy must be precisely controlled to prevent cellular dysfunction. The rapamycin-sensitive Tor kinase complex 1 (TORC1) has a major role in regulating the induction of autophagy; however, the regulatory mechanisms are not fully understood. Here, we find that Tap42 and protein phosphatase type 2A (PP2A) are involved in the regulation of autophagy in yeast. Temperature-sensitive mutant alleles of TAP42 revealed that autophagy was induced without inactivation of TORC1. Absence of the Tap42-interacting protein Tip41 abolished autophagy induction in the tap42 mutants, whereas overexpression of Tip41 activated autophagy. Furthermore, inactivation of PP2A stimulated autophagy and overexpression of a catalytic subunit of PP2A blocked rapamycin-induced autophagy. Our data support a model in which autophagy is negatively regulated by the Tap42-PP2A pathway.
authors.affiliation: Life Sciences Institute, Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yorimitsu
authors.forename: Congcong
authors.initials: C
authors.lastname: He
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D010588:Phagosomes / Q000201:enzymology; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C100984:TAP42 protein, S cerevisiae; C444301:TIP41 protein, S cerevisiae; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D054648:Protein Phosphatase 2; C104343:SIT4 protein, S cerevisiae