Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Cell. 2010 Aug 13;39(3):455-67. doi: 10.1016/j.molcel.2010.06.024. Epub 2010 Jul 1.
Progression through the Caulobacter cell cycle is driven by the master regulator CtrA, an essential two-component signaling protein that regulates the expression of nearly 100 genes. CtrA is abundant throughout the cell cycle except immediately prior to DNA replication. However, the expression of CtrA-activated genes is generally restricted to S phase. We identify the conserved protein SciP (small CtrA inhibitory protein) and show that it accumulates during G1, where it inhibits CtrA from activating target genes. The depletion of SciP from G1 cells leads to the inappropriate induction of CtrA-activated genes and, consequently, a disruption of the cell cycle. Conversely, the ectopic synthesis of SciP is sufficient to inhibit CtrA-dependent transcription, also disrupting the cell cycle. SciP binds directly to CtrA without affecting stability or phosphorylation; instead, SciP likely prevents CtrA from recruiting RNA polymerase. CtrA is thus tightly regulated by a protein-protein interaction which is critical to cell-cycle progression.
钙粘球菌细胞周期的进展由主调控因子 CtrA 驱动，CtrA 是一种必需的双组分信号蛋白，它调节近 100 个基因的表达。CtrA 在细胞周期中大量存在，除了在 DNA 复制之前。然而，CtrA 激活基因的表达通常局限于 S 期。我们鉴定了保守蛋白 SciP（小 CtrA 抑制蛋白），并表明它在 G1 期积累，在那里它抑制 CtrA 激活靶基因。从 G1 期细胞中耗尽 SciP 会导致 CtrA 激活基因的不当诱导，从而破坏细胞周期。相反，SciP 的异位合成足以抑制 CtrA 依赖性转录，也会破坏细胞周期。SciP 直接与 CtrA 结合，而不影响稳定性或磷酸化；相反，SciP 可能阻止 CtrA 招募 RNA 聚合酶。因此，CtrA 受到一种对细胞周期进展至关重要的蛋白质-蛋白质相互作用的严格调控。
