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首页> 外文期刊>Molecular and Cellular Biology >Human Progesterone Receptor Displays Cell Cycle-Dependent Changes in Transcriptional Activity
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Human Progesterone Receptor Displays Cell Cycle-Dependent Changes in Transcriptional Activity

机译：人类孕激素受体在转录活动中显示细胞周期依赖性变化。

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The human progesterone receptor (PR) contains multiple Ser-Pro phosphorylation sites that are potential substrates for cyclin-dependent kinases, suggesting that PR activity might be regulated during the cell cycle. Using T47D breast cancer cells stably transfected with an mouse mammary tumor virus (MMTV) chloramphenicol acetyltransferase reporter (Cat0) synchronized in different phases of the cell cycle, we found that PR function and phosphorylation is remarkably cell cycle dependent, with the highest activity in S phase. Although PR expression was reduced in the G2/M phase, the activity per molecule of receptor was markedly reduced in both G1 and G2/M phases compared to the results seen with the S phase of the cell cycle. Although PR is recruited to the MMTV promoter equivalently in the G1 and S phases, recruitment of SRC-1, SRC-3, and, consequently, CBP is reduced in G1 phase despite comparable expression levels of SRC-1 and SRC-3. In G2/M phase, site-specific phosphorylation of PR at Ser162 and at Ser294, a site previously reported to be critical for transcriptional activity and receptor turnover, was abolished. Treatment with the histone deacetylase inhibitor trichostatin A elevated G1 and G2/M activity to that of the S phase, indicating that the failure to recruit sufficient levels of active histone acetyltransferase is the primary defect in PR-mediated transactivation.
机译：人孕激素受体（PR）包含多个Ser-Pro磷酸化位点，这些位点是细胞周期蛋白依赖性激酶的潜在底物，表明PR活性可能在细胞周期中受到调节。使用稳定转染了小鼠乳腺肿瘤病毒（MMTV）氯霉素乙酰转移酶报告基因（Cat0）的T47D乳腺癌细胞在细胞周期的不同阶段同步，我们发现PR功能和磷酸化显着依赖于细胞周期，在S中具有最高的活性相。尽管在G 2 / M期PR表达降低，但在G 1 和G 2 中每分子受体的活性均明显降低。 / M相与细胞周期S期所见的结果相比。尽管PR在G 1 和S阶段等效地被征募到MMTV启动子，但S 1 的SRC-1，SRC-3和CBP的募集减少了。尽管SRC-1和SRC-3的表达水平相当，但仍>阶段。在G 2 / M期，Ser 162 和Ser 294 处PR的位点特异性磷酸化，以前据报道这对转录活性和受体转换被取消。用组蛋白脱乙酰基酶抑制剂曲古抑菌素A处理可将G 1 和G 2 / M活性提高至S期，表明未能募集足够水平的活性组蛋白乙酰转移酶是PR介导的反式激活的主要缺陷。

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