Ras proteins in the control of the cell cycle and cell differentiation

被引:160
作者
Crespo, P
León, J
机构
[1] Univ Cantabria, Fac Med, CSIC,Grp Biol Mol Canc, Unidad Asociada Ctr Invest Biol,Dept Biol Mol, E-39011 Santander, Spain
[2] CSIC, Inst Invest Biomed, Madrid, Spain
关键词
Ras; cell cycle; differentiation;
D O I
10.1007/PL00000645
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer: While constitutive Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15(INK4b), p16(INK4a), p19(ARF), and p21(WAF1) accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation,in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects of Ras in animal cells are discussed.
引用
收藏
页码:1613 / 1636
页数:24
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