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PXD009286-1

PXD009286 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleExpansion of DUB functionality by alternative isoforms: USP35, a case study
DescriptionProtein 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.
HostingRepositoryPRIDE
AnnounceDate2018-04-27
AnnouncementXMLSubmission_2018-04-27_06:37:29.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJayaprakash Natarajan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-03-21 08:47:54ID requested
12018-04-27 06:37:30announced
22024-10-22 04:44:11announced2024-10-22: 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 affiliationMRC Protein Phosphorylation and Ubiquitylation Unit School of Life Sciences, University of Dundee Sir James Black Centre Dundee, DD1 5EH United Kingdom
contact emailykulathu@dundee.ac.uk
lab head
Jayaprakash Natarajan
contact affiliationMRC PPU, University of Dundee
contact emailj.natarajan@dundee.ac.uk
dataset submitter
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