PXD038924

PXD038924 is an original dataset announced via ProteomeXchange.

Title	Activation of autophagy depends on Atg1/ULK1 mediated phosphorylation of the chaperone Hsp90
Description	The molecular chaperone Hsp90 is involved in the stability and activity of its client proteins which largely comprise of kinases. Phosphorylation of Hsp90 by these kinase clients provides a reciprocal regulatory mechanism between these proteins, however the mechanism of regulating the cellular pathway remains elusive. Here, we show that the serine/threonine kinase Atg1(yeast)/ULK1(mammalian) phosphorylates a conserved serine in the amino-domain of Hsp90 and reduces its ATPase activity hence lowers chaperone function. Broadly this modification negatively impacts the chaperoning of the kinase clients including Atg1/ULK1, yet enhances the activity of the non-kinase clients such as the heat shock factor and the steroid hormone receptors. Interestingly, ATG1/ULK1 mediated phosphorylation of the Hsp90 is essential for initiation of autophagy since yeast expressing a non-phosphorylatable Hsp90 were unable to undergo autophagy and the phosphomimetic Hsp90 mutants were underwent autophagy even in the absence of stimulus. Our findings provide a new paradigm where kinase client mediated phosphorylation of Hsp90 not only regulates the chaperone function but it is essential to initiate and regulate the relevant signaling pathway.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:02:52.974.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sarah Backe
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-19 03:40:09	ID requested
1	2023-09-08 14:08:12	announced
2	2023-11-14 09:05:09	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:02:53	announced	2024-10-22: Updated project metadata.

10.1016/j.celrep.2023.112807;

Backe SJ, Sager RA, Heritz JA, Wengert LA, Meluni KA, Aran-Guiu X, Panaretou B, Woodford MR, Prodromou C, Bourboulia D, Mollapour M, Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery. Cell Rep, 42(7):112807(2023) [pubmed]

submitter keyword: heat shock protein-90 (Hsp90), co-chaperone,Serine/threonine protein phosphatase-5 (PP5), SUMOylation, molecular chaperone, Phosphorylation

Mehdi Mollapour
contact affiliation	Department of Urology, SUNY Upstate Medical University Syracuse, NY 13210, USA
contact email	mollapom@upstate.edu
lab head
Sarah Backe
contact affiliation	SUNY Upstate Medical University
contact email	backes@upstate.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/09/PXD038924

PRIDE project URI

• PRIDE
  1. PXD038924
     1. Label: PRIDE project
     2. Name: Activation of autophagy depends on Atg1/ULK1 mediated phosphorylation of the chaperone Hsp90