The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Dev Cell. 2013 Jul 29;26(2):188-94. doi: 10.1016/j.devcel.2013.05.025. Epub 2013 Jul 11.
Methylation of nonhistone proteins is emerging as a regulatory mechanism to control protein function. Set7 (Setd7) is a SET-domain-containing lysine methyltransferase that methylates and alters function of a variety of proteins in vitro, but the in vivo relevance has not been established. We found that Set7 is a modifier of the Hippo pathway. Mice that lack Set7 have a larger progenitor compartment in the intestine, coinciding with increased expression of Yes-associated protein (Yap) target genes. Mechanistically, monomethylation of lysine 494 of Yap is critical for cytoplasmic retention. These results identify a methylation-dependent checkpoint in the Hippo pathway.
组蛋白以外蛋白质的甲基化正逐渐成为一种调控蛋白质功能的机制。Set7（Setd7）是一种含有 SET 结构域的赖氨酸甲基转移酶，它可以体外甲基化并改变多种蛋白质的功能，但尚未确定其在体内的相关性。我们发现 Set7 是 Hippo 途径的调节因子。缺乏 Set7 的小鼠肠道中的前体细胞区室更大，与 Yes 相关蛋白（Yap）靶基因的表达增加相一致。从机制上讲，Yap 的赖氨酸 494 单甲基化对于细胞质保留至关重要。这些结果确定了 Hippo 途径中的一个依赖于甲基化的检查点。
