Transcriptional profiling of the cell cycle checkpoint gene krüppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.
Transcriptional profiling of the cell cycle checkpoint gene krüppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.
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DOI：
10.3727/000000006783991908
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Yang VW
中科院分区：
文献类型：
--
作者：
Whitney EM;Ghaleb AM;Chen X;Yang VW
Krüppel样因子4（KLF 4;也称为肠道富集的Krüppel样因子或GKLF）已知在细胞周期的G1/S和G2/M转换期间表现出检查点功能。KLF 4发挥这些作用的机制尚未完全确定。在这里，我们研究了KLF 4在诱导系统中24小时内的表达谱。使用寡核苷酸微阵列，我们确定了KLF 4表达水平相对于对照的倍数变化在KLF 4诱导后4至24小时之间表现出时间依赖性的增加，从3倍增加到20倍。在此期间，在检测的473个细胞周期调控基因中，96个与KLF 4的表达谱呈正相关，86个与KLF 4的表达谱呈负相关。上调的细胞周期基因的实例包括编码肿瘤抑制因子如MCC和FHIT以及细胞周期抑制剂如CHES 1和CHEK 1的那些。下调基因的实例包括促进细胞周期的基因，包括几种细胞周期蛋白和DNA复制所需的基因。出乎意料的是，参与大分子合成的几组基因，包括蛋白质生物合成，转录和胆固醇生物合成，也被KLF 4显着抑制。因此，KLF 4对大分子生物合成发挥全面的抑制作用，这超出了其作为细胞周期抑制剂的既定作用。
Krüppel-like factor 4 (KLF4; also known as gut-enriched Krüppel-like factor or GKLF) is known to exhibit checkpoint function during the G1/S and G2/M transitions of the cell cycle. The mechanism by which KLF4 exerts these effects is not fully established. Here we investigated the expression profile of KLF4 in an inducible system over a time course of 24 h. Using oligonucleotide microarrays, we determined that the fold changes relative to control in expression levels of KLF4 exhibited a time-dependent increase from 3- to 20-fold between 4 and 24 h following KLF4 induction. During this period and among a group of 473 cell cycle regulatory genes examined, 96 were positively correlated and 86 were negatively correlated to KLF4's expression profile. Examples of upregulated cell cycle genes include those encoding tumor suppressors such as MCC and FHIT, and cell cycle inhibitors such as CHES1 and CHEK1. Examples of downregulated genes include those that promote the cell cycle including several cyclins and those required for DNA replication. Unexpectedly, several groups of genes involved in macromolecular synthesis, including protein biosynthesis, transcription, and cholesterol biosynthesis, were also significantly inhibited by KLF4. Thus, KLF4 exerts a global inhibitory effect on macromolecular biosynthesis that is beyond its established role as a cell cycle inhibitor.
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影响因子：
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作者：
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DOI：
10.1152/ajpgi.2000.279.4.g806
发表时间：
2000-10-01
影响因子：
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DOI：
10.1073/pnas.94.6.2156
发表时间：
1997-03-18
影响因子：
11.1
作者：
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通讯作者：
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