Everly David N, Mainou Bernardo A, Raab-Traub Nancy
Lineberger Comprehensive Cancer Center, CB#7295, University of North Carolina-Chapel Hill, 450 West Drive, Chapel Hill, NC 27599-7295, USA.
Virology. 2008 Jul 5;376(2):258-69. doi: 10.1016/j.virol.2007.12.003. Epub 2008 May 5.
LMP1 induces the expression of two members of the family of Id proteins, Id1 and Id3, and affects cell cycle regulation by decreasing the expression of the cyclin dependent kinase inhibitor, p27, and increasing levels and phosphorylation of cdk2 and Rb. In the present study, the contribution of the Id proteins to LMP1-mediated transformation was determined. Although LMP1 effectively inhibited p27 expression, the Id proteins alone did not affect expression of p27, cdk2, and Rb. Neither Id1 nor Id3 was sufficient to transform Rat-1 cells and inhibition of Id1 expression did not affect LMP1-induced morphologic transformation of Rat-1 cells or reduction of p27. However, reduced Id expression resulted in smaller foci and impaired the growth rate of Rat-1 cells. These data indicate that overexpression of the Id proteins is not sufficient for the effects of LMP1 on the cell cycle but that inhibition of Id expression does affect the growth of LMP1-transformed and parental Rat1 cells.
LMP1可诱导Id蛋白家族的两个成员Id1和Id3的表达,并通过降低细胞周期蛋白依赖性激酶抑制剂p27的表达,以及增加cdk2和Rb的水平及磷酸化来影响细胞周期调控。在本研究中,确定了Id蛋白对LMP1介导的细胞转化的作用。尽管LMP1有效抑制p27表达,但单独的Id蛋白并不影响p27、cdk2和Rb的表达。Id1和Id3均不足以转化Rat-1细胞,抑制Id1表达也不影响LMP1诱导的Rat-1细胞形态转化或p27的减少。然而,Id表达降低会导致较小的集落,并损害Rat-1细胞的生长速率。这些数据表明,Id蛋白的过表达不足以实现LMP1对细胞周期的影响,但抑制Id表达确实会影响LMP1转化的Rat1细胞和亲本Rat1细胞的生长。