The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription
Authors:Rubin Jiao1, Liubov Lobanova1, Amanda Waldner1, Anthony Fu1, Linda Xiao1, Troy A. Harkness1, and Terra G. Arnason1,2
doi: 10.15698/mic2016.11.538
Volume 3, pp. 540 to 553, published 05/11/2016.
1 Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
2 Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
Keywords:
SNF1 kinase, Ubc1, Forkheads, APC, protein stability.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no competing interests.
Please cite this article as:
Rubin Jiao, Liubov Lobanova, Amanda Waldner, Anthony Fu, Linda Xiao, Troy A. Harkness, and Terra G. Arnason (2016). The Ubiquitin-Conjugating Enzyme, Ubc1, Indirectly Regulates SNF1 Kinase Activity Via Forkhead-dependent Transcription. Microbial Cell 3(11): 540-553. doi: 10.15698/mic2016.11.538
© 2016 Jiao et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
The SNF1 kinase in Saccharomyces cerevisiae is 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 to SNF1 transcription. 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.