PXD041590-1

PXD041590 is an original dataset announced via ProteomeXchange.

Title	HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways
Description	HUWE1 is a large, enigmatic HECT domain ubiquitin ligase implicated in the degradation of numerous substrates and regulating diverse pathways including DNA repair, apoptosis, and differentiation. However, the mechanism by which HUWE1 acts in a pleiotropic manner to regulate a myriad of substrates is unknown. Recent work has established a physical and genetic interaction between HUWE1 and C16orf72/HAPSTR1, suggesting that HAPSTR1 positively regulates HUWE1 function. Here, we show that HAPSTR1 is both a HUWE1 substrate, and is required to localize HUWE1 to the nucleus. Quantitative proteomics across diverse cell types reveals that HUWE1 substrates are largely context specific. Transcriptomics following HUWE1 or HAPSTR1 loss of function reveals a broad transcriptional stress response. We show that nuclear HUWE1 impacts stress signaling pathways, including p53 and NFkB-mediated signaling, and is required for cell proliferation. Together, these data define a critical role for nuclear HUWE1 function that is dependent on HAPSTR1.
HostingRepository	PRIDE
AnnounceDate	2023-05-14
AnnouncementXML	Submission_2023-05-14_06:36:09.328.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	EricFischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-17 14:04:33	ID requested
⏵ 1	2023-05-14 06:36:10	announced
2	2023-11-14 08:48:11	announced	2023-11-14: Updated project metadata.

Monda JK, Ge X, Hunkeler M, Donovan KA, Ma MW, Jin CY, Leonard M, Fischer ES, Bennett EJ, HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways. Cell Rep, 42(5):112496(2023) [pubmed]

submitter keyword: ligase, substrates,HUWE1, HAPSTR1, ubiquitin

EricFischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
EricFischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.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/2023/05/PXD041590

PRIDE project URI

• PRIDE
  1. PXD041590
     1. Label: PRIDE project
     2. Name: HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways