PXD009286

PXD009286 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-21 08:47:54	ID requested
⏵ 1	2018-04-27 06:37:30	announced

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]

curator keyword: Biological

submitter keyword: apoptosis, Deubiquitinase, endoplasmic reticulum, lipid droplets, ubiquitin signalling

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

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PRIDE project URI

• PRIDE
  1. PXD009286
     1. Label: PRIDE project
     2. Name: Expansion of DUB functionality by alternative isoforms: USP35, a case study