Brady H J, Gil-Gómez G, Kirberg J, Berns A J
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
EMBO J. 1996 Dec 16;15(24):6991-7001.
Bax alpha can heterodimerize with Bcl-2 and Bcl-X(L), countering their effects, as well as promoting apoptosis on overexpression. We show that bax alpha transgenic mice have greatly reduced numbers of mature T cells, which results from an impaired positive selection in the thymus. This perturbation in positive selection is accompanied by an increase in the number of cycling thymocytes. Further to this, mature T cells overexpressing Bax alpha have lower levels of p27Kip1 and enter S phase more rapidly in response to interleukin-2 stimulation than do control T cells, while the converse is true of bcl-2 transgenic T cells. These data indicate that apoptotic regulatory proteins can modulate the level of cell cycle-controlling proteins and thereby directly impact on the cell cycle.
Baxα可与Bcl-2和Bcl-X(L)形成异二聚体,对抗它们的作用,并在过表达时促进细胞凋亡。我们发现,baxα转基因小鼠成熟T细胞数量大幅减少,这是由于胸腺中阳性选择受损所致。阳性选择的这种扰动伴随着循环胸腺细胞数量的增加。此外,过表达Baxα的成熟T细胞中p27Kip1水平较低,在白细胞介素-2刺激下比对照T细胞更快进入S期,而bcl-2转基因T细胞的情况则相反。这些数据表明,凋亡调节蛋白可调节细胞周期控制蛋白的水平,从而直接影响细胞周期。