title: The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription.
abstract: The SNF1 kinase inSaccharomyces cerevisiaeis an excellent model to study the regulation and function of the AMP-dependent protein kinase (AMPK) family of serine-threonine protein kinases. Yeast discoveries regarding the regulation of this non-hormonal sensor of metabolic/environmental stress are conserved in higher eukaryotes, including poly-ubiquitination of the α-subunit of yeast (Snf1) and human (AMPKα) that ultimately effects subunit stability and enzyme activity. The ubiquitin-cascade enzymes responsible for targeting Snf1 remain unknown, leading us to screen for those that impact SNF1 kinase function. We identified the E2, Ubc1, as a regulator of SNF1 kinase function. The decreased Snf1 abundance found upon deletion of Ubc1 is not due to increased degradation, but instead is partly due to impaired SNF1 gene expression, arising from diminished abundance of the Forkhead 1/2 proteins, previously shown to contribute toSNF1transcription. Ultimately, we report that the Fkh1/2 cognate transcription factor, Hcm1, fails to enter the nucleus in the absence of Ubc1. This implies that Ubc1 acts indirectly through transcriptional effects to modulate SNF1 kinase activity.
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Rubin
authors.initials: R
authors.lastname: Jiao
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Liubov
authors.initials: L
authors.lastname: Lobanova
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Amanda
authors.initials: A
authors.lastname: Waldner
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Anthony
authors.initials: A
authors.lastname: Fu
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Linda
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Harkness
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5. ; Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Terra G
authors.initials: TG
authors.lastname: Arnason
keywords: APC; Forkheads; SNF1 kinase; Ubc1; protein stability