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PXD050150-1

PXD050150 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life
DescriptionAuthors: David R. Amici, Sammy Alhayek, Austin T. Klein, Yi-Zhi Wang, Anika P. Wilen, Weimin Song, Pei Zhu, Abhishek Thakkar, McKenzi A. King, Adam Steffeck, Milad J. Alasady, Clara Peek, Jeffrey N. Savas, Marc L. Mendillo* ABSTRACT The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase which paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, while HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.
HostingRepositoryMassIVE
AnnounceDate2024-02-28
AnnouncementXMLSubmission_2024-02-28_08:34:10.192.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJeffrey N. Savas
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListTMTpro; Acetyl; Carboxymethyl; unknown modification
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-26 06:39:16ID requested
12024-02-28 08:34:10announced
Publication List
no publication
Keyword List
submitter keyword: HAPSTR1, HUWE1
Contact List
Marc L. Mendillo
contact affiliationNorthwestern University
contact emailmendillo@northwestern.edu
lab head
David R. Amici
contact affiliationNorthwestern University
contact emaildavid.amici@northwestern.edu
lab head
Jeffrey N. Savas
contact affiliationNorthwestern University
contact emailjeffrey.savas@northwestern.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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