Redundant targeting of Isr1 by two CDKs in mitotic cells.

Emma B Alme, David P Toczyski

Journal: Current genetics 2021;67(1):79-83

PMID: 33063175

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Abstract

Protein phosphorylation is an essential regulatory mechanism that controls most cellular processes, integrating a variety of environmental signals to drive cellular growth. Isr1 is a negative regulator of the hexosamine biosynthesis pathway (HBP), which produces UDP-GlcNAc, an essential carbohydrate that is the building block of N-glycosylation, GPI anchors and chitin. Isr1 was recently shown to be regulated by phosphorylation by the nutrient-responsive CDK kinase Pho85, allowing it to be targeted for degradation by the SCF. Here, we show that while deletion of PHO85 stabilizes Isr1 in asynchronous cells, Isr1 is still unstable in mitotically arrested cells in a pho85∆ strain. We provide evidence to suggest that this is through phosphorylation by CDK1. Redundant targeting of Isr1 by two distinct kinases may allow for tight regulation of the HBP in response to different cellular signals.

Address: Department of Biochemistry, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.; Department of Biochemistry, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA. [email protected].

DOI: 10.1007/s00294-020-01110-x

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MeSH Terms: Biosynthetic Pathways, CDC2 Protein Kinase, Cell Cycle, Cell Cycle Proteins, Cyclin-Dependent Kinases, F-Box Proteins, Glucosamine, Glycosylation, Hexosamines, Mitosis, Phosphorylation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitin-Protein Ligases