ClpC and MecA, components of a proteolytic machine, prevent Spo0A-P-dependent transcription without degradation.
ClpC and MecA, components of a proteolytic machine, prevent Spo0A-P-dependent transcription without degradation.
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ClpC 和 MecA 是蛋白水解机的组成部分，可防止 Spo0A-P 依赖性转录而不发生降解。
DOI：
10.1111/mmi.13928
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发表时间：
2018
影响因子：
3.6
通讯作者：
Dubnau,David
中科院分区：
文献类型：
--
作者：
Tanner,AndrewW;Carabetta,ValerieJ;Dubnau,David
在枯草芽孢杆菌中，由MecA、ClpC和ClpP组成的蛋白水解机器降解转录因子ComK，控制其在生长期间的积累。MecA还通过下调spoIIG和sinI抑制孢子形成和生物膜形成，这些基因依赖于磷酸化蛋白Spo 0A-P的转录。此外，MecA已被证明与Spo 0A在体外相互作用。虽然对转录的抑制作用需要MecA的结合伴侣ClpC，但抑制并不伴随着Spo 0A的降解，这表明涉及这些蛋白质的先前未被怀疑的调控机制。在这里，我们进一步研究了MecA和ClpC对Spo 0A-P-依赖性转录的影响。我们发现MecA抑制了几个Spo 0A-P激活基因的转录，但未能去抑制几个Spo 0A-P抑制的启动子。这表明MecA和ClpC不通过阻止Spo 0A-P与其靶启动子的结合而起作用。与此一致，MecA本身对PspoIIG的体外转录没有影响，而加入MecA和ClpC两者具有强抑制作用。MecA和ClpC的复合物可能与其靶启动子上的Spo 0A-P结合，阻止转录的激活。因此，降解机器的组件已经被利用来直接抑制转录。
InBacillus subtilis, a proteolytic machine composed of MecA, ClpC and ClpP degrades the transcription factor ComK, controlling its accumulation during growth. MecA also inhibits sporulation and biofilm formation by down‐regulatingspoIIGandsinI, genes that are dependent for their transcription on the phosphorylated protein Spo0A‐P. Additionally, MecA has been shown to interactin vitrowith Spo0A. Although the inhibitory effect on transcription requires MecA's binding partner ClpC, inhibition is not accompanied by the degradation of Spo0A, pointing to a previously unsuspected regulatory mechanism involving these proteins. Here, we further investigate the MecA and ClpC effects on Spo0A‐P‐dependent transcription. We show that MecA inhibits the transcription of several Spo0A‐P activated genes, but fails to de‐repress several Spo0A‐P repressed promoters. This demonstrates that MecA and ClpC do not act by preventing the binding of Spo0A‐P to its target promoters. Consistent with this, MecA by itself has no effectin vitroon the transcription from PspoIIGwhile the addition of both MecA and ClpC has a strong inhibitory effect. A complex of MecA and ClpC likely binds to Spo0A‐P on its target promoters, preventing the activation of transcription. Thus, components of a degradative machine have been harnessed to directly repress transcription.