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PXD012229

PXD012229 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePost-translational Regulation of FNIP1: a Rheostat for the Molecular Chaperone Hsp90
DescriptionThe molecular chaperone Hsp90 stabilizes and activates client proteins. Co-chaperones and post-translational modifications tightly regulate Hsp90 function and consequently lead to activation of clients. However, it is unclear whether this process occurs abruptly or gradually in the cellular context. We show that casein kinase-2 phosphorylation of the co-chaperone Folliculin-interacting protein-1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90. This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients. We further demonstrate that serine/threonine protein phosphatase-5 (PP5) dephosphorylates FNIP1, allowing addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938. This process antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 lysine-1119 ubiquitination and proteasomal degradation. These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
HostingRepositoryPRIDE
AnnounceDate2019-01-31
AnnouncementXMLSubmission_2019-02-07_04:08:52.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMehdi Mollapour
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentTOF/TOF 5800
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-01-03 03:53:08ID requested
12019-01-31 00:34:14announced
22019-02-07 04:08:53announcedUpdated publication reference for PubMed record(s): 30699359.
Publication List
Sager RA, Woodford MR, Backe SJ, Makedon AM, Baker-Williams AJ, DiGregorio BT, Loiselle DR, Haystead TA, Zachara NE, Prodromou C, Bourboulia D, Schmidt LS, Linehan WM, Bratslavsky G, Mollapour M, Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90. Cell Rep, 26(5):1344-1356.e5(2019) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: Heat Shock Protein-90 (Hsp90), Co-chaperone, FNIP1, Folliculin-interacting protein-1, Serine/threonine protein phosphatase-5, PP5, O-GlcNAcylation
Contact List
Mehdi Mollapour
contact affiliationDepartment of Urology, SUNY Upstate Medical University Syracuse, NY 13210, USA
contact emailmollapom@upstate.edu
lab head
Mehdi Mollapour
contact affiliationSUNY Upstate Medical University
contact emailmollapom@upstate.edu
dataset submitter
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Dataset FTP location
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