PXD056564-1

PXD056564 is an original dataset announced via ProteomeXchange.

Title	Functional landscape of ubiquitin linkages couples K29-linked ubiquitylation to epigenome integrity
Description	Linkage-specific ubiquitin chains govern the outcome of numerous critical ubiquitin-dependent signaling processes. However, the targets and functional impacts of linkage-specific ubiquitin modifications remain incompletely understood, due to a paucity of tools for their specific detection and manipulation. Here, we applied a cell-based ubiquitin replacement strategy enabling targeted conditional abrogation of each of the seven lysine-based ubiquitin linkages in human cells to profile system-wide impacts of disabling formation of individual chain types. This revealed proteins and processes regulated by each of these poly-ubiquitin topologies and established indispensable roles of K48-, K63- and K27-linkages, but not K6-, K11-, K29- and K33-linkages, in cell proliferation. We show that K29-linked ubiquitylation is strongly associated with chromosome biology, and that the H3K9me3 methyltransferase SUV39H1 is a prominent cellular target of this modification. K29-linked ubiquitylation catalyzed by TRIP12 and reversed by TRABID constitutes the essential degradation signal for SUV39H1 and is primed and extended by Cullin-RING ubiquitin ligase activity. Preventing K29-linked ubiquitylation-mediated control of SUV39H1 stability deregulates H3K9me3 homeostasis but not other histone modifications. Collectively, these data resources illuminate cellular functions of linkage-specific ubiquitin chains and establish a key role of K29-linked ubiquitylation in epigenome integrity.
HostingRepository	PRIDE
AnnounceDate	2025-10-21
AnnouncementXML	Submission_2025-10-21_06:31:27.557.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-07 16:42:57	ID requested
⏵ 1	2025-10-21 06:31:28	announced

10.1038/S44318-025-00599-7;

submitter keyword: K29, epigenome maintenance,TRIP12,ubiquitylation

Matthias Mann
contact affiliation	1 Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry,Germany. 2 NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056564
     1. Label: PRIDE project
     2. Name: Functional landscape of ubiquitin linkages couples K29-linked ubiquitylation to epigenome integrity