Cytokine response gene 6 induces p21 and regulates both cell growth and arrest
Cytokine response gene 6 induces p21 and regulates both cell growth and arrest
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DOI：
10.1038/sj.onc.1203054
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发表时间：
1999-11-11
期刊：
影响因子：
8
通讯作者：
Smith, KA
中科院分区：
文献类型：
--
作者：
Fan, W;Richter, G;Smith, KA
细胞因子应答基因#6（Cytokine response gene #6，CR 6）是从白细胞介素2刺激的T淋巴细胞中克隆的，与促进细胞周期停滞和凋亡的基因GADD 45和MyD 118同源。为了确定该基因家族如何可能介导细胞存活/增殖和细胞周期停滞/死亡，产生转染子，使得基因可以异位表达，而不依赖于它们的正常诱导剂。在周期性视网膜母细胞瘤蛋白阴性（pRb-）细胞中，异位CR 6表达阻断G2/M转换，但不阻止G1/S转换，从而导致核内复制。与此相一致的是，当CR 6、GADD 45和MyD 118基因在增殖的pRb（+）细胞中异位表达时，G1/S或G2/M转换被有效地阻断，因此没有核内复制。G1期细胞周期蛋白表达增加，有丝分裂期细胞周期蛋白表达减少。然而，在pRb（+）细胞中，与G1和G2/M细胞周期蛋白相关的细胞周期蛋白依赖性激酶活性降低。此外，所有三个基因的异位表达导致CKI、p21在pRb-和pRb（+）细胞中的表达。IL 2对静止期正常人T细胞CR 6表达的生理性诱导在G1的前半期短暂发生，与p21的表达协调。因此，该基因家族调节G1和G2，并通过共同的机制促进细胞生长或停滞。
Cytokine response gene #6 (CR6), cloned from interleukin 2-stimulated T lymphocytes, is homologous to GADD45 and MyD118, genes which promote cell cycle arrest and apoptosis, To determine how this gene family could possibly mediate both cell survival/proliferation and cell cycle arrest/death, transfectants were generated so that the genes could be expressed ectopically, independently from their normal inducing agents. In cycling retinoblastoma protein-negative (pRb-) cells, ectopic CR6 expression blocked G2/M transition, but did not prevent G1/S transition so that endoreduplication resulted. By comparison, when CR6, GADD45, and MyD118 genes were expressed ectopically in proliferating pRb(+) cells, either G1/S or G2/M transition was effectively blocked, so that there was no endoreduplication, Consistent with these findings, in proliferating pRb-cells, ectopic expression of CR6 promoted the expression of both G1 and G2/M cyclins, By comparison, in pRb+ cells, the expression of G1 cyclins was increased, while expression of the mitotic cyclins was decreased. However, in pRb(+) cells, cyclin-dependent kinase activities associated with both G1 and G2/M cyclins were decreased. Moreover, ectopic expression of all three genes resulted in the expression of the CKI, p21, both in pRb- and pRb(+) cells. The physiologic induction of CR6 expression by IL2 in quiescent normal human T cells occurs transiently in the first half of G1, coordinately with the expression of p21, Therefore, this gene family regulates G1 and G2, and promotes either cell growth or arrest by a common mechanism.