PXD050150-1
PXD050150 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life |
| Description | Authors: 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-02-28 |
| AnnouncementXML | Submission_2024-02-28_08:34:10.192.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Jeffrey N. Savas |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | TMTpro; Acetyl; Carboxymethyl; unknown modification |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-02-26 06:39:16 | ID requested | |
| ⏵ 1 | 2024-02-28 08:34:10 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: HAPSTR1, HUWE1 |
Contact List
| Marc L. Mendillo | |
|---|---|
| contact affiliation | Northwestern University |
| contact email | mendillo@northwestern.edu |
| lab head | |
| David R. Amici | |
| contact affiliation | Northwestern University |
| contact email | david.amici@northwestern.edu |
| lab head | |
| Jeffrey N. Savas | |
| contact affiliation | Northwestern University |
| contact email | jeffrey.savas@northwestern.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v07/MSV000094168/ |
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