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The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription

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 c...

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Detalles Bibliográficos
Autores principales: Jiao, Rubin, Lobanova, Liubov, Waldner, Amanda, Fu, Anthony, Xiao, Linda, Harkness, Troy A., Arnason, Terra G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349210/
https://www.ncbi.nlm.nih.gov/pubmed/28357323
http://dx.doi.org/10.15698/mic2016.11.538
Descripción
Sumario: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.