EXPRESSION AND STATE OF PHOSPHORYLATION OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE-PRODUCT IN CYCLING AND NONCYCLING HUMAN HEMATOPOIETIC-CELLS
EXPRESSION AND STATE OF PHOSPHORYLATION OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE-PRODUCT IN CYCLING AND NONCYCLING HUMAN HEMATOPOIETIC-CELLS
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DOI：
10.1073/pnas.87.7.2770
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发表时间：
1990-04-01
影响因子：
11.1
通讯作者：
GRIFFIN, JD
中科院分区：
文献类型：
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作者：
FURUKAWA, Y;DECAPRIO, JA;GRIFFIN, JD
视网膜母细胞瘤易感基因RB1（Rb）的产物可能作为细胞生长的抑制剂发挥作用。先前的研究表明，Rb的某些生长抑制作用在G0/G1期发挥，并且磷酸化可使这些功能失活。我们通过检测在几种自发停滞在G0期的原代造血细胞系中Rb的表达和磷酸化状态来验证这一假设。静止的淋巴细胞仅表达未磷酸化的Rb，但当细胞响应有丝分裂原进入S期时，Rb会发生磷酸化。相比之下，尽管单核细胞和粒细胞也高水平表达未磷酸化的Rb，但这些终末分化的细胞不会使Rb磷酸化，它们也不会响应生长因子从G1期退出。因此，Rb磷酸化似乎与细胞合成DNA的能力相关。在T细胞和B细胞中，受刺激后Rb蛋白增加8倍，而RB1 RNA水平增加2 - 4倍。T细胞中的核连缀分析和RB1 RNA半衰期的测量表明，RNA丰度增加至少部分是由于RNA稳定性增加。相比之下，受刺激后单核细胞和粒细胞中的Rb蛋白水平均未增加，尽管单核细胞中的RB1 RNA水平确实增加了。因此，在淋巴细胞和髓细胞中，Rb磷酸化的调节以及RB1基因表达均存在谱系特异性差异。
The product of the retinoblastoma susceptibility gene RB1 (Rb) is likely to function as an inhibitor of cell growth. Previous studies have suggested that certain growth suppressing effects of Rb are exerted in G0/G1 phase and that phosphorylation can inactive these functions. We tested this hypothesis by examining the expression and state of phosphorylation of Rb in several lineages of primary hematopoietic cells that spontaneously arrest in G0 phase. Resting, lymphocytes were found to express only unphosphorylated Rb, but phosphorylating of Rb occurred as the cells entered S phase in response to mitogens. In contrast, although monocytes and granulocytes also expressed high levels of unphosphorylated Rb, these terminally differentiated cells did not phosphorylate Rb, nor could they exit from G1 phase in response to growth factors. Thus, Rb phosphorylation appears linked to the ability of a cell to synthesize DNA. In T and B lymphocytes, Rb protein increased 8-fold after stimulation, while RB1 RNA levels increased 2- to 4-fold. Nuclear run-on assays and measurement of RB1 RNA half-life in T cells suggested that the increased RNA abundance was, at least in part, due to increased RNA stability. By contrast, Rb protein levels did not increase in either monocytes or granlocytes after stimulation, although RB1 RNA levels did increase in monocytes. Thus, they are lineage-specific differences in both the regulation of Rb phosphorylation and RB1 gene expression in lymphoid and myeloid cells.