Proteomics

Dataset Information

82

Converging SUMO and ubiquitin signaling: improved methodology identifies co-modified target proteins


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo sapiens  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Sabine Cuijpers  

LAB HEAD: Alfred C.O. Vertegaal

PROVIDER: PXD007733 | Pride | 2017-09-29

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
HUMAN.fasta Fasta
Other files.rar Other
QE_SC_double_SU_U2OS12221099_DMSO_BR1_TR1.raw Raw
QE_SC_double_SU_U2OS12221099_DMSO_BR1_TR2.raw Raw
QE_SC_double_SU_U2OS12221099_DMSO_BR1_TR3.raw Raw
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Publications

Converging Small Ubiquitin-like Modifier (SUMO) and Ubiquitin Signaling: Improved Methodology Identifies Co-modified Target Proteins.

Cuijpers Sabine A G SAG   Willemstein Edwin E   Vertegaal Alfred C O ACO  

Molecular & cellular proteomics : MCP 20170926 12


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. Because little is known about crosstalk among different ubiquitin family members, we developed an improved method enabling identification of co-modified proteins  ...[more]

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