Departments of Pathology, Genetics, and Biology, Stanford University, Stanford, CA 94305-5324, USA.
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Biol Open. 2020 May 7;9(5):bio051508. doi: 10.1242/bio.051508.
The five-protein MuvB core complex is highly conserved in animals. This nuclear complex interacts with RB-family tumor suppressor proteins and E2F-DP transcription factors to form DREAM complexes that repress genes that regulate cell cycle progression and cell fate. The MuvB core complex also interacts with Myb family oncoproteins to form the Myb-MuvB complexes that activate many of the same genes. We show that animal-type genes are present in Bilateria, Cnidaria and Placozoa, the latter including the simplest known animal species. However, bilaterian nematode worms lost their animal-type genes hundreds of millions of years ago. Nevertheless, amino acids in the LIN9 and LIN52 proteins that directly interact with the MuvB-binding domains of human B-Myb and Myb are conserved in Here, we show that, despite greater than 500 million years since their last common ancestor, the Myb protein can bind to the nematode LIN9-LIN52 proteins and can cause a synthetic multivulval (synMuv) phenotype This phenotype is similar to that caused by loss-of-function mutations in synMuvB-class genes including those that encode homologs of the MuvB core, RB, E2F and DP. Furthermore, amino acid substitutions in the MuvB-binding domain of Myb that disrupt its functions and also disrupt these activities in We speculate that nematodes and other animals may contain another protein that can bind to LIN9 and LIN52 in order to activate transcription of genes repressed by DREAM complexes.
五蛋白 MuvB 核心复合物在动物中高度保守。这种核复合物与 RB 家族肿瘤抑制蛋白和 E2F-DP 转录因子相互作用，形成 DREAM 复合物，抑制调节细胞周期进程和细胞命运的基因。MuvB 核心复合物还与 Myb 家族癌蛋白相互作用，形成 Myb-MuvB 复合物，激活许多相同的基因。我们表明，动物型 基因存在于两侧对称动物、刺胞动物和扁盘动物中，后者包括已知最简单的动物物种。然而，两侧对称的线虫蠕虫在数亿年前就失去了它们的动物型 基因。尽管如此，与人类 B-Myb 和 Myb 的 MuvB 结合域直接相互作用的 LIN9 和 LIN52 蛋白中的氨基酸在 中是保守的。在这里，我们表明，尽管它们的最后共同祖先已经超过 5 亿年，但 Myb 蛋白可以与线虫 LIN9-LIN52 蛋白结合，并可以引起合成多育（synMuv）表型 这种表型类似于 MuvB 类基因缺失功能突变引起的表型，包括编码 MuvB 核心、RB、E2F 和 DP 同源物的基因。此外， Myb 的 MuvB 结合域中的氨基酸取代破坏了其功能 也破坏了 中的这些活性。我们推测，线虫和其他动物可能含有另一种可以与 LIN9 和 LIN52 结合的蛋白质，以激活 DREAM 复合物抑制的基因的转录。
