PXD007733

PXD007733 is an original dataset announced via ProteomeXchange.

Title	Converging SUMO and ubiquitin signaling: improved methodology identifies co-modified target proteins
Description	Post translational protein modifications (PTMs) including small chemical groups and small proteins, belonging to the ubiquitin family, are essential for virtually all cellular processes. In addition to modification by a single PTM, proteins can be modified by a combination of different modifiers, which are able to influence each other. Since little is known about crosstalk between different ubiquitin family members, we developed an improved method enabling identification of co-modified proteins on a system-wide level using mass spectrometry. We focused on the role of crosstalk between SUMO and ubiquitin during proteasomal degradation. Using two complementary approaches, we identified 498 proteins to be significantly co-modified by SUMO and ubiquitin upon MG132 treatment. These targets included many enzymatic components of PTM machinery, involved in SUMOylation and ubiquitylation, but also phosphorylation, methylation and acetylation, revealing a highly complex interconnected network of crosstalk between different PTMs. In addition various other biological processes were found to be significantly enriched within the group of co-modified proteins, including transcription, DNA repair and the cell cycle. Interestingly, the latter group mostly consisted of proteins involved in mitosis, including a subset of chromosome segregation regulators. We hypothesize that group modification by SUMO-targeted ubiquitin ligases regulates the stability of the identified subset of mitotic proteins, which ensures proper chromosome segregation. The mitotic regulators KIF23 and MIS18BP1 were verified to be co-modified by SUMO and ubiquitin upon inhibition of the proteasome and subsequently identified as novel RNF4 targets. Both modifications on MIS18BP1 were observed to increase simultaneously during late mitosis, while the total protein level decreased immediately afterwards. These results confirm the regulation of MIS18BP1 via SUMO-ubiquitin crosstalk during mitosis. Combined, our work highlights extensive crosstalk between SUMO and ubiquitin, providing a resource for further unraveling of SUMO-ubiquitin crosstalk.
HostingRepository	PRIDE
AnnounceDate	2017-09-29
AnnouncementXML	Submission_2017-09-29_07:39:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sabine Cuijpers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-13 01:31:31	ID requested
⏵ 1	2017-09-29 07:39:45	announced

Cuijpers SAG, Willemstein E, Vertegaal ACO, Converging Small Ubiquitin-like Modifier (SUMO) and Ubiquitin Signaling: Improved Methodology Identifies Co-modified Target Proteins. Mol Cell Proteomics, 16(12):2281-2295(2017) [pubmed]

curator keyword: Technical, Biological

submitter keyword: PTMs, SUMO, ubiquitin, co-modification, human, nanoLC-MS/MS

Alfred C.O. Vertegaal
contact affiliation	Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
contact email	vertegaal@lumc.nl
lab head
Sabine Cuijpers
contact affiliation	Leiden University Medical Center
contact email	s.a.g.cuijpers@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007733
     1. Label: PRIDE project
     2. Name: Converging SUMO and ubiquitin signaling: improved methodology identifies co-modified target proteins