PXD009286 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Expansion of DUB functionality by alternative isoforms: USP35, a case study |
Description | Protein ubiquitylation is a dynamic post-translational modification that can be reversed by deubiquitylating enzymes (DUBs). It is unclear how the small number of ~100 DUBs present in mammalian cells regulates the thousands of different ubiquitylation events. Here we analysed annotated transcripts of human DUBs and find ~300 ribosome-associated transcripts annotated as protein coding, which thus increase the total number of DUBs. Using USP35, a poorly studied DUB, as a case study we provide evidence that alternative isoforms contribute to the functional expansion of DUBs. We show the existence of two different USP35 isoforms that localise to different intracellular compartments and have distinct functions. Our results reveal that isoform 1 is an anti-apoptotic factor that inhibits staurosporine- and TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. In contrast, USP35 isoform 2 is an integral membrane protein of the endoplasmic reticulum (ER) present also at lipid droplets. Manipulations of isoform 2 levels cause rapid ER stress likely through deregulation of lipid homeostasis and lead to cell death. Our work highlights how alternative isoforms provide functional expansion of DUBs and sets directions for future research. |
HostingRepository | PRIDE |
AnnounceDate | 2018-04-27 |
AnnouncementXML | Submission_2018-04-27_06:37:29.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jayaprakash Natarajan |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-03-21 08:47:54 | ID requested | |
⏵ 1 | 2018-04-27 06:37:30 | announced | |
2 | 2024-10-22 04:44:11 | announced | 2024-10-22: Updated project metadata. |
Publication List
Leznicki P, Natarajan J, Bader G, Spevak W, Schlattl A, Abdul Rehman SA, Pathak D, Weidlich S, Zoephel A, Bordone MC, Barbosa-Morais NL, Boehmelt G, Kulathu Y, Expansion of DUB functionality generated by alternative isoforms - USP35, a case study. J Cell Sci, 131(10):(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: apoptosis, Deubiquitinase, endoplasmic reticulum, lipid droplets, ubiquitin signalling |
Contact List
Yogesh Kulathu |
contact affiliation | MRC Protein Phosphorylation and Ubiquitylation Unit School of Life Sciences, University of Dundee Sir James Black Centre Dundee, DD1 5EH United Kingdom |
contact email | ykulathu@dundee.ac.uk |
lab head | |
Jayaprakash Natarajan |
contact affiliation | MRC PPU, University of Dundee |
contact email | j.natarajan@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009286
- Label: PRIDE project
- Name: Expansion of DUB functionality by alternative isoforms: USP35, a case study