DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.
DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.
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DOI：
10.1016/j.devcel.2014.01.028
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发表时间：
2014-03-31
影响因子：
11.8
通讯作者：
Antebi, Adam
中科院分区：
文献类型：
--
作者：
Horn, Moritz;Geisen, Christoph;Cermak, Lukas;Becker, Ben;Nakamura, Shuhei;Klein, Corinna;Pagano, Michele;Antebi, Adam
发育定时基因催化跨类群的干细胞进展和动物成熟程序。C.秀丽线虫DRE-1/FBXO 11在SCF E3-泛素连接酶复合物中发挥功能，调节向成体程序的转变，但其同源蛋白水解底物尚不清楚。在这里，我们确定了保守的锌指转录因子BLMP-1作为SCFDRE-1/FBXO 11复合物的底物。BLMP-1功能丧失抑制DRE-1突变表型，并表现出与DRE-1相反的发育时间缺陷。blmp-1也反对dre-1的其他生活史特征，包括进入dauer滞育和寿命。BLMP-1蛋白在dre-1耗竭后显著升高，并以阶段和组织特异性方式失调。DRE-1在调节BLMP-1稳定性中的作用是进化保守的，因为我们观察到蠕虫和人类对应物的直接蛋白质相互作用和降解功能。综上所述，DRE-1/FBXO 11对BLMP-1/BLIMP-1的翻译后调节与C. elegans发育时间和其他生活史性状，表明这两个蛋白质模块介导后生动物的成熟过程。
Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. C. 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 Zn-finger transcription factor BLMP-1 as a substrate of the SCFDRE-1/FBXO11 complex. blmp-1 loss-of-function 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, post-translational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting this two-protein-module mediates metazoan maturation processes.
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影响因子：
50.3
作者：
Mandelbaum J;Bhagat G;Tang H;Mo T;Brahmachary M;Shen Q;Chadburn A;Rajewsky K;Tarakhovsky A;Pasqualucci L;Dalla-Favera R
通讯作者：
Dalla-Favera R
影响因子：
3.3
作者：
Cai, Qingchun;Sun, Yinyan;Zhang, Hong
通讯作者：
Zhang, Hong
影响因子：
56.9
作者：
AMBROS, V;HORVITZ, HR
通讯作者：
HORVITZ, HR
DOI：
10.1073/pnas.1217271110
发表时间：
2013-03-05
影响因子：
11.1
作者：
Chiorazzi, Michael;Rui, Lixin;Staudt, Louis M.
通讯作者：
Staudt, Louis M.
影响因子：
64.5
作者：
Ohinata, Yasuhide;Ohta, Hiroshi;Saitou, Mitinori
通讯作者：
Saitou, Mitinori