Díaz Víctor M, Mori Silvia, Longobardi Elena, Menendez Guillermo, Ferrai Carmelo, Keough Rebecca A, Bachi Angela, Blasi Francesco
Molecular Genetics Unit, Department of Molecular Biology and Functional Genomics, Università Vita Salute San Raffaele and DIBIT, H San Raffaele, via Olgettina 58, 20132 Milan, Italy.
Mol Cell Biol. 2007 Nov;27(22):7981-90. doi: 10.1128/MCB.01290-07. Epub 2007 Sep 17.
Prep1 is known to interact in vivo with Pbx1 to regulate development and organogenesis. We have identified a novel Prep1-interacting protein, p160 c-Myb binding protein (p160). p160 and Pbx1 compete for Prep1 in vitro, and p160 inhibits Prep1-dependent HoxB2 expression in retinoic acid-treated NT2-D1 cells. The N-terminal physiologically truncated form of p160, p67, binds the sequence 63LFPLL67 in the HR1 domain of Prep1. Mutation of both L63 and L66 impairs the binding of Prep1 to both p160/p67 and Pbx1. The sequences required to bind Prep1 are mainly located in residues 51 to 151. Immunofluorescence colocalization and coimmunoprecipitation of endogenous p160 and Prep1 are induced by ActD, which translocates p160 from the nucleolus to the nucleoplasm. These data therefore show that p160 is a novel regulator of Prep1-Pbx1 transcriptional activity.
已知Prep1在体内与Pbx1相互作用以调节发育和器官发生。我们鉴定出一种新型的与Prep1相互作用的蛋白,即p160 c-Myb结合蛋白(p160)。p160和Pbx1在体外竞争Prep1,并且p160在视黄酸处理的NT2-D1细胞中抑制Prep1依赖性的HoxB2表达。p160的N端生理性截短形式p67与Prep1的HR1结构域中的序列63LFPLL67结合。L63和L66的突变会损害Prep1与p160/p67和Pbx1的结合。结合Prep1所需的序列主要位于第51至151位残基中。放线菌素D诱导内源性p160和Prep1的免疫荧光共定位和免疫共沉淀,放线菌素D将p160从核仁转运至核质。因此,这些数据表明p160是Prep1-Pbx1转录活性的新型调节因子。