Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Dev Cell. 2010 Jan 19;18(1):90-101. doi: 10.1016/j.devcel.2009.10.024.
NAD(H)-binding proteins play important roles in cell-cycle and developmental signaling in eukaryotes. We identified a bifunctional NAD(H)-binding regulator (KidO) that integrates cell-fate signaling with cytokinesis in the bacterium Caulobacter crescentus. KidO stimulates the DivJ kinase and directly acts on the cytokinetic tubulin, FtsZ, to tune cytokinesis with the cell cycle. At the G1-->S transition, DivJ concomitantly signals the ClpXP-dependent degradation of KidO and CtrA, a cell-cycle transcriptional regulator/DNA replication inhibitor. This proteolytic event directs KidO and CtrA into oscillatory cell-cycle abundance patterns that coordinately license replication and cytokinesis. KidO resembles NAD(P)H-dependent oxidoreductases, and conserved residues in the KidO NAD(H)-binding pocket are critical for regulation of FtsZ, but not for DivJ. Since NADPH-dependent regulation by a KidO-like oxidoreductase also occurs in humans, organisms from two domains of life exploit the enzymatic fold of an ancestral oxidoreductase potentially to coordinate cellular or developmental activities with the availability of the metabolic currency, NAD(P)H.
NAD(H)结合蛋白在真核生物的细胞周期和发育信号转导中发挥重要作用。我们鉴定了一种双功能 NAD(H)结合调节剂（KidO），它将细胞命运信号与细菌新月柄杆菌的胞质分裂整合在一起。KidO 刺激 DivJ 激酶，并直接作用于细胞分裂的微管蛋白 FtsZ，以调节细胞周期与胞质分裂。在 G1-->S 过渡期间，DivJ 同时发出依赖于 ClpXP 的 KidO 和 CtrA 的降解信号，CtrA 是细胞周期转录调节剂/DNA 复制抑制剂。这种蛋白水解事件将 KidO 和 CtrA 定向进入振荡的细胞周期丰度模式，协调复制和胞质分裂的许可。KidO 类似于 NAD(P)H 依赖性氧化还原酶，KidO NAD(H)结合口袋中的保守残基对于 FtsZ 的调节至关重要，但对于 DivJ 则不是。由于人类中也存在 NADPH 依赖性 KidO 样氧化还原酶的调节，因此来自两个生命领域的生物利用了祖先氧化还原酶的酶折叠，可能将细胞或发育活动与代谢货币 NAD(P)H 的可用性协调起来。
