Richon V M, Rifkind R A, Marks P A
DeWitt Wallace Research Laboratory, Memorial Sloan-Kettering Cancer Center, Cornell University, New York, New York 10021.
Cell Growth Differ. 1992 Jul;3(7):413-20.
Phosphorylation and dephosphorylation of the retinoblastoma protein, pRB, play a role in the control of cell cycle progression and expression of differentiation in eukaryotic cells. The regulation of pRB level and phosphorylation state was investigated during the induction of differentiation of murine erythroleukemia cells (MELC) by the chemical agent hexamethylene bisacetamide (HMBA). In MELC, there is a critical time in G1 or early S phase when HMBA must be present in order to induce differentiation. This is followed by prolongation of the subsequent G1 phase, resumption of progression through the cell cycle for several generations, and then cell cycle arrest in G1-G0. Associated with HMBA-induced prolongation of G1, there is an increase in the amount of the underphosphorylated form of pRB. A variant cell line (DS19/VCR-C) with accelerated kinetics of HMBA-mediated differentiation shows a more marked increase in underphosphorylated pRB. In culture with HMBA, as MELC resume progression through the cell cycle, pRB is present in the phosphorylated form. The total amount of pRB increases approximately 3-fold over the succeeding cell divisions prior to terminal arrest in G1. This increase in pRB is inhibited by dexamethasone, which also blocks HMBA-induced MELC differentiation. During this period, RB mRNA also increases approximately 3- to 5-fold, which reflects an increase in the rate of transcription, with no change in mRNA stability. The state of phosphorylation and amount of pRB appear to be involved in the control of HMBA-induced terminal cell division of MELC.
视网膜母细胞瘤蛋白pRB的磷酸化和去磷酸化在真核细胞的细胞周期进程控制和分化表达中发挥作用。我们研究了化学试剂六亚甲基双乙酰胺（HMBA）诱导小鼠红白血病细胞（MELC）分化过程中pRB水平和磷酸化状态的调节。在MELC中，G1期或早期S期存在一个关键时间点，此时必须存在HMBA才能诱导分化。随后是随后的G1期延长，细胞周期连续几代恢复进程，并最终在G1-G0期停滞。与HMBA诱导的G1期延长相关，pRB的低磷酸化形式的量增加。具有加速的HMBA介导分化动力学的变异细胞系（DS19/VCR-C）显示低磷酸化pRB的增加更为明显。在HMBA培养中，随着MELC恢复细胞周期进程，pRB以磷酸化形式存在。在G1期终末停滞之前的后续细胞分裂过程中，pRB的总量增加了约3倍。pRB的这种增加受到地塞米松的抑制，地塞米松也阻断HMBA诱导的MELC分化。在此期间，RB mRNA也增加了约3至5倍，这反映了转录速率的增加，而mRNA稳定性没有变化。pRB的磷酸化状态和量似乎参与了HMBA诱导的MELC终末细胞分裂的控制。
