PXD018429

PXD018429 is an original dataset announced via ProteomeXchange.

Title	The kinase Isr1 negatively regulates hexosamine biosynthesis in S. cerevisiae
Description	The S. cerevisiae ISR1 gene encodes a putative kinase with no ascribed function. Here, we show that Isr1 acts as a negative regulator of the highly conserved hexosamine biosynthesis pathway (HBP), which converts glucose into uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the carbohydrate precursor to protein glycosylation, GPI-anchor formation and chitin biosynthesis. Overexpression of Isr1 is lethal and, at lower levels, causes sensitivity to tunicamycin and resistance to calcofluor white, implying impaired protein glycosylation and reduced chitin deposition. GFA1 is the first enzyme in the HBP and is conserved from bacteria and yeast to humans. Isr1 lethality is rescued by overexpression of GFA1 or exogenous glucosamine, which bypasses GFA1's essential function. Gfa1 is phosphorylated in an ISR1-dependent fashion and mutation of Isr1-dependent sites ameliorates the lethality associated with Isr1 overexpression. Isr1 contains a phosphodegron that is phosphorylated by Pho85 and subsequently ubiquitinated by the SCF -Cdc4 complex, largely confining Isr1 protein levels to the time of bud emergence. Mutation of this phosphodegron stabilizes Isr1 and recapitulates the overexpression phenotypes. As Pho85 is a cell cycle and nutrient responsive kinase, this tight regulation of Isr1 may serve to dynamically regulate flux through the HBP and modulate how the cell’s energy resources are converted into structural carbohydrates in response to changing cellular needs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:06:51.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Danielle Swaney
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	phosphorylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-08 15:44:55	ID requested
1	2020-06-06 18:30:17	announced
⏵ 2	2024-10-22 05:06:51	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: DIA, phosphoproteomics,yeast, timsTOF Pro

Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
lab head
Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018429
     1. Label: PRIDE project
     2. Name: The kinase Isr1 negatively regulates hexosamine biosynthesis in S. cerevisiae