Inhibitory function of p21Cip1/WAF1 in differentiation of primary mouse keratinocytes independent of cell cycle control
Inhibitory function of p21Cip1/WAF1 in differentiation of primary mouse keratinocytes independent of cell cycle control
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DOI：
10.1126/science.280.5366.1069
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发表时间：
1998-05-15
期刊：
影响因子：
56.9
通讯作者：
Dotto, GP
中科院分区：
文献类型：
--
作者：
Di Cunto, F;Topley, G;Dotto, GP
细胞周期蛋白依赖性激酶抑制剂p21（Cip 1/WAF 1）被认为是分化诱导剂。然而，尽管在紧邻增殖区室的有丝分裂后细胞中p21的表达增加，但其表达在进一步沿着分化程序的细胞中降低。p21蛋白的表达在小鼠的终末分化的原代角质形成细胞中降低，并且这是通过蛋白酶体依赖性途径发生的。p21在这些细胞中的强制表达在蛋白质和信使RNA水平上抑制了终末分化标志物的表达。这些对分化的抑制作用没有观察到与羧基末端截短突变体或与无关的细胞周期蛋白依赖性激酶抑制剂p16（INK 4a），虽然所有这些分子产生类似的细胞生长抑制。这些发现揭示了p21在分化后期的抑制作用，而不是由于p21对细胞周期的影响。
The cyclin-dependent kinase inhibitor p21(Cip1/WAF1) has been implicated as an inducer of differentiation. However, although expression of p21 is increased in postmitotic cells immediately adjacent to the proliferative compartment, its expression is decreased in cells further along the differentiation program. Expression of the p21 protein was decreased in terminally differentiated primary keratinocytes of mice, and this occurred by a proteasome-dependent pathway. Forced expression of p21 in these cells inhibited the expression of markers of terminal differentiation at both the protein and messenger RNA levels. These inhibitory effects on differentiation were not observed with a carboxyl-terminal truncation mutant or with the unrelated cyclin-dependent kinase inhibitor p16(INK4a), although all these molecules exerted similar inhibition of cell growth. These findings reveal an inhibitory role of p21 in the late stages of differentiation that does not result from the effects of p21 on the cell cycle.