THE RETINOBLASTOMA GENE-PRODUCT REGULATES PROGRESSION THROUGH THE G1 PHASE OF THE CELL-CYCLE

THE RETINOBLASTOMA GENE-PRODUCT REGULATES PROGRESSION THROUGH THE G1 PHASE OF THE CELL-CYCLE
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DOI:
10.1016/0092-8674(91)90181-w
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发表时间:
1991-10-18
期刊:
影响因子:
64.5
通讯作者:
LEE, WH
LEE, WH
中科院分区:
生物学1区
文献类型:
--
作者:
GOODRICH, DW;WANG, NP;LEE, WH

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RB基因产物是一种核磷酸化蛋白,其磷酸化状态发生细胞周期依赖性变化。为了测试RB是否调节细胞周期进程,将纯化的RB蛋白(全长或含有T抗原结合区的截短形式)注射到细胞中。G1期早期注射任意一种蛋白均可抑制病程进展至S期。联合注射抗rb抗体可拮抗这种作用。将RB注射到G1/S期或G1后期的细胞中,对BrdU的掺入没有影响,表明RB不抑制S期DNA合成。这些结果表明RB通过在G1的特定点限制细胞周期进程来调节细胞增殖,并建立了RB活性的生物学测定方法。无论是将RB与T抗原肽共同注射,还是将其注射到表达T抗原的细胞中,都不能阻止细胞进入S期,这支持了T抗原结合对RB有功能影响的假设。
The RB gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To test whether RB regulates cell cycle progression, purified RB proteins, either full-length or a truncated form containing the T antigen-binding region, were injected into cells. Injection of either protein early in G1 inhibits progression into S phase. Co-injection of anti-RB antibodies antagonizes this effect. Injection of RB into cells arrested at G1/S or late in G1 has no effect on BrdU incorporation, suggesting that RB does not inhibit DNA synthesis in S phase. These results indicate that RB regulates cell proliferation by restricting cell cycle progression at a specific point in G1 and establish a biological assay for RB activity. Neither co-injection of RB with a T antigen peptide nor injection into cells expressing T antigen prevents cells from progressing into S phase, which supports the hypothesis that T antigen binding has functional consequences for RB.