DOI number:10.1016/j.celrep.2023.113145
Journal:Cell Rep.
Abstract:The conserved WD40-repeat protein WDR5 interacts with multiple proteins both inside and outside the nucleus. However, it is currently unclear whether and how the distribution ofWDR5 between complexes is regulated. Here, we show that an unannotatedmicroprotein EMBOW (endogenous microprotein binder of WDR5) dually encoded in the human SCRIB gene interacts with WDR5 and regulates its binding to multiple interaction partners, including KMT2A and KIF2A. EMBOW is cell cycle regulated, with two expression maxima at late G1 phase and G2/M phase. Loss of EMBOW decreases WDR5 interaction with KIF2A, aberrantly shortens mitotic spindle length, prolongs G2/M phase, and delays cell proliferation. In contrast, loss of EMBOW increases WDR5 interaction with KMT2A, leading to WDR5 binding to off-target genes, erroneously increasing H3K4me3 levels, and activating transcription of these genes. Together, these results implicate EMBOW as a regulator of WDR5 that regulates its interactions and prevents its off-target binding in multiple contexts.
Co-author:Jianing Zhao, Zhenkun Na, Kevin Jiang, Antonella Bacchiocchi, Ken H. Loh, Ruth Halaban, Zhentian Wang
First Author:Yanran Chen, Haomiao Su
Indexed by:Journal paper
Correspondence Author:Xiongwen Cao, Sarah A. Slavoff
Document Code:113145
Discipline:Natural Science
Document Type:J
Volume:42
Issue:0
Page Number:113145
Translation or Not:no
Date of Publication:2023-09-26
Included Journals:SCI
Links to published journals:https://www.sciencedirect.com/science/article/pii/S2211124723011579?via%3Dihub