Ume6 transcription factor is part of a signaling cascade that regulates autophagy.
Autophagy has been implicated in a number of physiological processes important for human heath and disease. Autophagy involves the formation of a double-membrane cytosolic vesicle, an autophagosome. Central to the formation of the autophagosome is the ubiquitin-like protein autophagy-related (Atg)8 (microtubule-associated protein 1 light chain 3/LC3 in mammalian cells). Following autophagy induction, Atg8 shows the greatest change in expression of any of the proteins required for autophagy. The magnitude of autophagy is, in part, controlled by the amount of Atg8; thus, controlling Atg8 protein levels is one potential mechanism for modulating autophagy activity. We have identified a negative regulator of ATG8 transcription, Ume6, which acts along with a histone deacetylase complex including Sin3 and Rpd3 to regulate Atg8 levels; deletion of any of these components leads to an increase in Atg8 and a concomitant increase in autophagic activity. A similar regulatory mechanism is present in mammalian cells, indicating that this process is highly conserved.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Clinton R
CR
Bartholomew
Tsukasa
T
Suzuki
Zhou
Z
Du
Steven K
SK
Backues
Meiyan
M
Jin
Melinda A
MA
Lynch-Day
Midori
M
Umekawa
Avani
A
Kamath
Mantong
M
Zhao
Zhiping
Z
Xie
Ken
K
Inoki
Daniel J
DJ
Klionsky
D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D017353:Gene Deletion; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000378:metabolism; D014158:Transcription, Genetic; D014617:Vacuoles / Q000378:metabolism
C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C089979:UME6 protein, S cerevisiae; D011494:Protein Kinases; C410736:Rim15 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex