PXD052680

PXD052680 is an original dataset announced via ProteomeXchange.

Title	APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons
Description	Non-degradative histone ubiquitylation plays myriad well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but molecular mechanism are unclear. Here we show that despite directly binding to the nucleosome through subunit APC3, the APC/C is unable to ubiquitylate nucleosomal histones. In contrast, extranucleosomal H2A/H2B and H3/H4 complexes are broadly ubiquitylated by the APC/C. Using a combination of cryo-electron microscopy (cryo-EM) and biophysical and enzymatic assays, we demonstrate that APC8 and histone tails direct APC/C-mediated polyubiquitylation of core histones in the absence of traditional APC/C substrate degron sequences. Our work implicates APC/C-nucleosome tethering in regulated degradation of diverse chromatin-associated proteins and extranucleosomal histones for the regulation of transcription and the cell cycle and for preventing toxicity due to excess histone levels.
HostingRepository	PRIDE
AnnounceDate	2025-03-17
AnnouncementXML	Submission_2025-03-17_15:34:33.600.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dennis Goldfarb
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; propanoylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-29 12:09:44	ID requested
⏵ 1	2025-03-17 15:34:33	announced

10.1038/S41467-025-57384-7;

submitter keyword: ubiquitylation,Nucelosomes

Robert McGinty
contact affiliation	Department of Biochemistry and Biophysics, UNC School of Medicine, University of North Carolina, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
contact email	rmcginty@email.unc.edu
lab head
Dennis Goldfarb
contact affiliation	Cell Biology and Physiology Institute for Informatics
contact email	d.goldfarb@wustl.edu
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/2025/03/PXD052680

PRIDE project URI

• PRIDE
  1. PXD052680
     1. Label: PRIDE project
     2. Name: APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons