PXD010430

PXD010430 is an original dataset announced via ProteomeXchange.

Title	Tetrahydrobiopterin modulates ubiquitin conjugation to UBC13/UBE2N and proteasome activity by S-nitrosation
Description	Nitric Oxide (NO) is an intracellular signalling mediator, which affects many biological processes via the posttranslational modification of proteins through S-nitrosation. The availability of NO and NOS-derived reactive oxygen species (ROS) from enzymatic uncoupling are determined by the NO synthase cofactor Tetrahydrobiopterin (BH4). Here, using a global proteomics “biotin-switch” approach, we identified components of the ubiquitin-proteasome system to be altered via BH4-dependent NO signalling by protein S-nitrosation. We show S-nitrosation of ubiquitin conjugating E2 enzymes, in particular the catalytic residue C87 of UBC13/UBE2N, leading to impaired polyubiquitylation by interfering with the formation of UBC13~Ub thioester intermediates. In addition, proteasome cleavage activity in cells also seems to be altered by S-nitrosation, correlating with the modification of cysteine residues within the 19S regulatory particle and catalytic subunits of the 20S complex. Our results highlight the widespread impact of BH4 on downstream cellular signalling as evidenced by the effect of a perturbed BH4-dependent NO-Redox balance on critical processes within the ubiquitin-proteasome system (UPS). These studies thereby uncover a novel aspect of NO associated modulation of cellular homeostasis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:46:27.238.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD010430
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Deamidated; Oxidation; DeStreak; Carbamidomethyl
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-13 07:35:27	ID requested
1	2018-10-02 07:20:48	announced
2	2019-02-12 07:36:42	announced	Updated publication reference for PubMed record(s): 30254268.
⏵ 3	2024-10-22 04:46:29	announced	2024-10-22: Updated project metadata.

10.1038/s41598-018-32481-4;

Bailey J, Davis S, Shaw A, Diotallevi M, Fischer R, Benson MA, Zhu H, Brown J, Bhattacharya S, Kessler BM, Channon KM, Crabtree MJ, Tetrahydrobiopterin modulates ubiquitin conjugation to UBC13/UBE2N and proteasome activity by S-nitrosation. Sci Rep, 8(1):14310(2018) [pubmed]

10.6019/PXD010430;

curator keyword: Biological

submitter keyword: biotin switch,S-nitrosylation

Roman Fischer
contact affiliation	Head of Discovery Proteomics Facility, Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010430
     1. Label: PRIDE project
     2. Name: Tetrahydrobiopterin modulates ubiquitin conjugation to UBC13/UBE2N and proteasome activity by S-nitrosation