Steinman R A, Huang J, Yaroslavskiy B, Goff J P, Ball E D, Nguyen A
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Steinman+@pitt.edu
Blood. 1998 Jun 15;91(12):4531-42.
The G1-phase cell-cycle inhibitor p21 has been proposed to mediate growth arrest during differentiation. Upregulation of p21 has been shown in multiple cell lines induced to differentiate; however, the mechanism of p21 induction during normal differentiation is largely unknown. In this report, we use normal hematopoietic precursor cells obtained from umbilical cord to model p21 regulation during differentiation. Myeloid maturation of CD34+ precursor cells is associated with a marked increase in p21 expression at the RNA and protein level. The upregulation of p21 transcripts during differentiation is associated with decreased binding to a highly conserved 44-bp fragment within the p21 promoter. This 44-bp regulatory element binds a novel modulator of p21 expression. It is of considerable interest that, although the binding activity is expressed in p53-negative as well as in p53-positive cells, the DNA sequence recognized by this protein overlaps a PuPuPuC(A/T)(T/A)GPyPyPy consensus sequence for p53.
G1期细胞周期抑制剂p21被认为在分化过程中介导生长停滞。在多种诱导分化的细胞系中已显示p21上调；然而，正常分化过程中p21诱导的机制很大程度上尚不清楚。在本报告中，我们使用从脐带获得的正常造血前体细胞来模拟分化过程中的p21调控。CD34+前体细胞的髓系成熟与RNA和蛋白质水平上p21表达的显著增加相关。分化过程中p21转录本的上调与p21启动子内一个高度保守的44碱基对片段的结合减少有关。这个44碱基对的调控元件结合了一种p21表达的新型调节因子。值得关注的是，尽管这种结合活性在p53阴性和p53阳性细胞中均有表达，但该蛋白识别的DNA序列与p53的PuPuPuC(A/T)(T/A)GPyPyPy共有序列重叠。
