PXD041519-3

PXD041519 is an original dataset announced via ProteomeXchange.

Title	Orphan quality control shapes network dynamics and gene expression
Description	All eukaryotes require intricate protein networks to translate developmental signals into accurate cell fate decisions. Mutations that disturb interactions between network components often result in disease, but how composition and dynamics of complex networks are established remains poorly understood. Here, we identify the E3 ligase UBR5 as a signaling hub that helps degrade unpaired subunits of multiple transcriptional regulators that act within a network centered on the c-MYC oncoprotein. Biochemical and structural analyses show that UBR5 binds motifs that only become available upon complex dissociation. By rapidly turning over orphan transcription factor subunits, UBR5 establishes dynamic interactions between transcriptional regulators that allow cells to effectively execute gene expression, while remaining receptive to environmental signals. We conclude that orphan quality control plays an essential role in establishing dynamic protein networks, which may explain the conserved need for protein degradation during transcription and offers unique opportunities to modulate gene expression in disease. Crosslinking mass spec experiment with UBR5 HECT domain STREP-SUMO-MCRS1 and DSSO.
HostingRepository	PRIDE
AnnounceDate	2024-11-01
AnnouncementXML	Submission_2024-11-01_08:57:36.823.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jan Seebacher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	crosslinked residues with loss of water; crosslinked L-lysine residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-13 07:56:30	ID requested
1	2023-05-30 07:20:19	announced
2	2024-10-22 05:45:56	announced	2024-10-22: Updated project metadata.
⏵ 3	2024-11-01 08:57:37	announced	2024-11-01: Updated project metadata.

10.1016/j.cell.2023.06.015;

Mark KG, Kolla S, Aguirre JD, Garshott DM, Schmitt S, Haakonsen DL, Xu C, Kater L, Kempf G, Mart, í, nez-Gonz, á, lez B, Akopian D, See SK, Thom, ä NH, Rap, é M, Orphan quality control shapes network dynamics and gene expression. Cell, 186(16):3460-3475.e23(2023) [pubmed]

submitter keyword: MYC, DSSO, UBR5, proteasome,ubiquitin, orphan quality control, crosslinking

Nicolas Holger Thoma
contact affiliation	Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
contact email	nicolas.thoma@fmi.ch
lab head
Jan Seebacher
contact affiliation	FMI Basel
contact email	jan.seebacher@fmi.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/05/PXD041519

PRIDE project URI

• PRIDE
  1. PXD041519
     1. Label: PRIDE project
     2. Name: Orphan quality control shapes network dynamics and gene expression