Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany.
Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany.
Dev Cell. 2014 Mar 31;28(6):697-710. doi: 10.1016/j.devcel.2014.01.028. Epub 2014 Mar 6.
Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits, including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, as we observed direct protein interaction and degradation function for worm and human counterparts. Taken together, posttranslational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting that this two-protein module mediates metazoan maturation processes.
发育时间基因在不同分类单元中催化干细胞进展和动物成熟程序。秀丽隐杆线虫 DRE-1/FBXO11 在 SCF E3-泛素连接酶复合物中发挥作用,以调节向成年程序的转变,但它的同源蛋白水解底物尚不清楚。在这里,我们鉴定了保守的转录因子 BLMP-1 作为 SCF(DRE-1/FBXO11) 复合物的底物。blmp-1 缺失抑制了 dre-1 突变体的表型,并表现出与 dre-1 相反的发育时间缺陷。blmp-1 也与 dre-1 对其他生活史特征相反,包括进入 dauer 休眠和长寿。BLMP-1 蛋白在 dre-1 耗竭时显著升高,并以阶段和组织特异性的方式失调。DRE-1 在调节 BLMP-1 稳定性方面的作用是进化保守的,因为我们观察到了线虫和人类对应物之间的直接蛋白质相互作用和降解功能。总之,DRE-1/FBXO11 对 BLMP-1/BLIMP-1 的翻译后调控协调了秀丽隐杆线虫的发育时间和其他生活史特征,表明该双蛋白模块介导了后生动物的成熟过程。