Transcriptional control of cell-cycle quiescence during C. elegans development
Transcriptional control of cell-cycle quiescence during C. elegans development
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DOI：
10.1016/j.ydbio.2007.10.051
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发表时间：
2008-01-15
影响因子：
2.7
通讯作者：
Saito, R. Mako
中科院分区：
文献类型：
--
作者：
Clayton, Joseph E.;van den Heuvel, Sander J. L.;Saito, R. Mako
在线虫生殖系统的发育过程中，产生外阴的细胞--外阴前体细胞(VPC)--在两个幼虫阶段保持静止，然后在第三个幼虫阶段恢复细胞分裂。我们已经确定了几个转录调控因子，它们促成了这种暂时的细胞周期停滞。LIN-1或LIN-31是控制VPC细胞命运的受体酪氨酸激酶(RTK)/RAS/MAP激酶级联反应的两个下游靶点，它们的突变破坏了VPC的暂时静止。我们发现，LIN-1/Ets和LIN-31/FoxB转录因子促进细胞周期蛋白依赖性激酶抑制物(CKIs)p27家族成员CKI-1的表达。LIN-1和LIN-31通过激活RTK/RAS/MAPK促进CKI-11KIP-1转录，然后抑制其转录。在筛查中发现的另一个突变定义了MDT-13 TRAP240介体亚单位。对多亚基介体复合体的进一步分析表明，其组件的特定子集在vPC静止时起作用。这些组分基本上与转录抑制所涉及的CDK-8模块重叠。综上所述，VPC发育过程中细胞周期停滞的严格控制涉及CKI-1的转录诱导和通过中介复合体的转录调控。这些转录调控因子代表了发育和基本细胞周期机制之间潜在的分子联系。(C)2007 Elsevier Inc.保留所有权利。
During the development of the C elegans reproductive system, cells that give rise to the vulva, the vulval precursor cells (VPCs), remain quiescent for two larval stages before resuming cell division in the third larval stage. We have identified several transcriptional regulators that contribute to this temporary cell-cycle arrest. Mutation of lin-1 or lin-31, two downstream targets of the Receptor Tyrosine kinase (RTK)/Ras/MAP kinase cascade that controls VPC cell fate, disrupts the temporary VPC quiescence. We found that the LIN-1/Ets and LIN-31/FoxB transcription factors promote expression of CKI-1, a member of the p27 family of cyclin-dependent kinase inhibitors (CKIs). LIN-1 and LIN-31 promote cki-11 Kip-1 transcription prior to their inhibition through RTK/Ras/MAPK activation. Another mutation identified in the screen defined the mdt-13 TRAP240 Mediator subunit. Further analysis of the multi-subunit Mediator complex revealed that a specific subset of its components act in VPC quiescence. These components substantially overlap with the CDK-8 module implicated in transcriptional repression. Taken together, strict control of cell-cycle quiescence during VPC development involves transcriptional induction of CKI-1 and transcriptional regulation through the Mediator complex. These transcriptional regulators represent potential molecular connections between development and the basic cell-cycle machinery. (C) 2007 Elsevier Inc. All rights reserved.