Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks.

Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks.
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DOI:
10.1016/j.molcel.2011.07.018
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发表时间:
2011-08-19
期刊:
影响因子:
16
通讯作者:
Jenal U
Jenal U
中科院分区:
生物学1区
文献类型:
--
作者:
Abel S;Chien P;Wassmann P;Schirmer T;Kaever V;Laub MT;Baker TA;Jenal U

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在新月形Caulobacter crescent中,关键调控因子的磷酸化与第二信使环di-GMP协调,驱动细胞周期的进展和分化。二胍酸环化酶PleD指导极形态形成,而c-二gmp效应物PopA通过AAA+蛋白酶ClpXP启动复制抑制剂CtrA的降解,从而允许s期进入。在这里,我们建立了依赖于磷酸二酯酶PdeA和二胍酸环化酶DgcB的PleD和PopA之间的直接联系。PdeA拮抗DgcB活性直至G1-S转变,此时PdeA被ClpXP蛋白酶降解。无对抗DgcB活性,与PleD激活一起,提高c-di-GMP,以驱动依赖于popa的CtrA降解和s相进入。PdeA降解需要CpdR, CpdR是一种反应调节因子,以磷酸化依赖的方式将PdeA传递给ClpXP蛋白酶。因此,CpdR作为磷酸化途径和c-di-GMP代谢之间的关键纽带,介导蛋白质降解事件,不可逆地协调驱动细菌细胞周期的进展和发育。
In Caulobacter crescentus, phosphorylation of key regulators is coordinated with the second messenger cyclic di-GMP to drive cell cycle progression and differentiation. The diguanylate cyclase PleD directs pole morphogenesis while the c-di-GMP effector PopA initiates degradation of the replication inhibitor CtrA by the AAA+ protease ClpXP to license S-phase entry. Here we establish a direct link between PleD and PopA reliant on the phosphodiesterase PdeA and the diguanylate cyclase DgcB. PdeA antagonizes DgcB activity until the G1-S transition when PdeA is degraded by the ClpXP protease. The unopposed DgcB activity, together with PleD activation, upshifts c-di-GMP to drive PopA-dependent CtrA degradation and S-phase entry. PdeA degradation requires CpdR, a response regulator that delivers PdeA to the ClpXP protease in a phosphorylation-dependent manner. Thus, CpdR serves as a crucial link between phosphorylation pathways and c-di-GMP metabolism to mediate protein degradation events that irreversibly and coordinately drive bacterial cell cycle progression and development.
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