PDF(Pubmed)
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 of WDR5 between complexes is regulated. Here, we show that an unannotated microprotein 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.
摘要：
保守的WD40重复蛋白WDR5与细胞核内外的多种蛋白相互作用。然而,目前尚不清楚WDR5在复合物之间的分布是否以及如何受到调控.这里,我们表明，在人SCRIB基因中双重编码的未注释的微蛋白EMBOW（WDR5的内源性微蛋白结合剂）与WDR5相互作用，并调节其与多个相互作用伙伴的结合，包括KMT2A和KIF2A。脑膜受细胞周期调节，在G1期晚期和G2/M期有两个表达最大值。EMBOW的丢失减少了WDR5与KIF2A的相互作用，异常缩短有丝分裂纺锤体长度，延长G2/M期，并延迟细胞增殖。相比之下,丧失EMBOW增加了WDR5与KMT2A的相互作用，导致WDR5与脱靶基因结合，错误地增加H3K4me3水平，并激活这些基因的转录。一起,这些结果提示EMBOW是WDR5的调节因子,调节其相互作用并防止其在多种情况下的脱靶结合.
