Gartel A L, Goufman E, Tevosian S G, Shih H, Yee A S, Tyner A L
Department of Molecular Genetics, University of Illinois at Chicago, 60607, USA.
Oncogene. 1998 Dec 31;17(26):3463-9. doi: 10.1038/sj.onc.1202240.
The Cdk inhibitor p21(WAF1/CIP1) is a negative regulator of the cell cycle, although its expression is induced by a number of mitogens that promote cell proliferation. We have found that E2F1 and E2F3, transcription factors that activate genes required for cell cycle progression, are strong activators of the p21 promoter. In contrast, HBP1 (HMG-box protein-1), a novel retinoblastoma protein-binding protein, can repress the p21 promoter and inhibit induction of p21 expression by E2F. Both E2Fs and HBP1 regulate p21 transcription through cis-acting elements located between nucleotides -119 to +16 of the p21 promoter and the DNA binding domains of each of these proteins are required for activity. Sequences between -119 and -60 basepairs containing four Sp1 consensus elements and two noncanonical E2F binding sites are of major importance for E2F activation, although E2F1 and E2F3 differ in the extent of their ability to activate expression when this segment is deleted. The opposing effects of E2Fs and HBP1 on p21 promoter activity suggest that interplay between these factors may determine the level of p21 transcription in vivo.
细胞周期蛋白依赖性激酶抑制剂p21（WAF1/CIP1）是细胞周期的负调控因子，尽管其表达是由多种促进细胞增殖的有丝分裂原诱导产生的。我们发现，激活细胞周期进程所需基因的转录因子E2F1和E2F3是p21启动子的强激活剂。相反，一种新型的视网膜母细胞瘤蛋白结合蛋白HBP1（HMG盒蛋白-1）可以抑制p21启动子，并抑制E2F对p21表达的诱导。E2F和HBP1都通过位于p21启动子核苷酸-119至+16之间的顺式作用元件调节p21转录，并且这些蛋白质各自的DNA结合结构域对于活性是必需的。包含四个Sp1共有元件和两个非典型E2F结合位点的-119至-60碱基对之间的序列对于E2F激活至关重要，尽管当该片段缺失时，E2F1和E2F3激活表达的能力程度有所不同。E2F和HBP1对p21启动子活性的相反作用表明，这些因子之间的相互作用可能决定体内p21转录的水平。
