HCF-1 promotes cell cycle progression by regulating the expression of CDC42.

HCF-1 promotes cell cycle progression by regulating the expression of CDC42.
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DOI:
10.1038/s41419-020-03094-5
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发表时间:
2020-10-23
影响因子:
9
通讯作者:
Peng X
Peng X
中科院分区:
生物学1区
文献类型:
--
作者:
Xiang P;Li F;Ma Z;Yue J;Lu C;You Y;Hou L;Yin B;Qiang B;Shu P;Peng X

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真核细胞周期涉及一系列高度协调的事件,其中细胞基因组在合成(S)期复制,并且两个所得拷贝中的每一个在有丝分裂(M)期间适当地分离。宿主细胞因子-1(HCF-1)是一种转录辅助调节因子,它对基本的细胞过程(如转录调节和细胞周期进程)至关重要,并与之有关。虽然已经鉴定了一系列HCF-1转录靶点,但很少提供功能线索,特别是染色体分离。我们的研究结果表明,HCF-1通过与CDC 42转录起始位点上游的-881至575区域结合来激活CDC 42的表达,并且HCF-1对CDC 42表达的调节与细胞周期进程相关。自发循环和组成型活性CDC 42突变体(CDC 42 F28 L)的过表达挽救了HCF-1缺失后有丝分裂中的G1期延迟和多核缺陷。因此,这些结果表明,HCF-1通过调节CDC 42的表达来确保适当的细胞周期进程,这表明细胞周期协调的可能机制和典型Rho GTP酶的调节模式。
The eukaryotic cell cycle involves a highly orchestrated series of events in which the cellular genome is replicated during a synthesis (S) phase and each of the two resulting copies are segregated properly during mitosis (M). Host cell factor-1 (HCF-1) is a transcriptional co-regulator that is essential for and has been implicated in basic cellular processes, such as transcriptional regulation and cell cycle progression. Although a series of HCF-1 transcriptional targets have been identified, few functional clues have been provided, especially for chromosome segregation. Our results showed that HCF-1 activated CDC42 expression by binding to the −881 to −575 region upstream of the CDC42 transcription start site, and the regulation of CDC42 expression by HCF-1 was correlated with cell cycle progression. The overexpression of a spontaneously cycling and constitutively active CDC42 mutant (CDC42F28L) rescued G1 phase delay and multinucleate defects in mitosis upon the loss of HCF-1. Therefore, these results establish that HCF-1 ensures proper cell cycle progression by regulating the expression of CDC42, which indicates a possible mechanism of cell cycle coordination and the regulation mode of typical Rho GTPases.
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