PXD036699

PXD036699 is an original dataset announced via ProteomeXchange.

Title	Unannotated microprotein EMBOW switches WDR5 between epigenetic and mitotic roles during cell cycle
Description	The highly conserved WD40-repeat protein WDR5 is part of multiple functional complexes both inside and outside the nucleus, interacting with the MLL/SET1 histone methyltransferases that catalyze histone H3 lysine 4 (H3K4) di- and tri-methylation (me2,3), and KIF2A, a member of the Kinesin-13 family of microtubule depolymerase. It is currently unclear whether, and how, the distribution of WDR5 between complexes is regulated. Here, we show that an unannotated microprotein dually encoded in the human SCRIB gene regulates the association of WDR5 with epigenetic and KIF2A complexes. We propose to name this alt-protein EMBOW, or microprotein that is the epigenetic to mitotic binder of WDR5. Loss of EMBOW decreases WDR5 interaction with KIF2A, displaces WDR5 from the spindle pole during G2/M phase, and shortens the spindle length, hence prolonging G2/M phase and delaying cell proliferation. On the other hand, loss of EMBOW increases WDR5 interaction with epigenetic complexes, including KMT2A/MLL1, and promotes WDR5 association with chromatin and binding to the target genes, hence increasing H3K4me3 levels of target genes. Together, these results implicate EMBOW as a regulator of WDR5 that switches it between epigenetic and mitotic regulatory roles during cell cycle, explaining how mammalian cells can temporally control the multifunctionality of WDR5.
HostingRepository	PRIDE
AnnounceDate	2023-09-19
AnnouncementXML	Submission_2023-09-19_02:15:48.709.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	xiongwencao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-14 02:18:34	ID requested
⏵ 1	2023-09-19 02:15:49	announced

submitter keyword: HEK 293T cells,human, LC-MS/MS

Sarah A.Slavoff
contact affiliation	Department of Chemistry, Yale University, New Haven, CT, USA
contact email	sarah.slavoff@yale.edu
lab head
xiongwencao
contact affiliation	Yale University, Chemical Biology Institute
contact email	xiongwen.cao@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036699
     1. Label: PRIDE project
     2. Name: Unannotated microprotein EMBOW switches WDR5 between epigenetic and mitotic roles during cell cycle