在不同的肿瘤中,通过干扰RB1信号通路,生长控制失去了正常调节。
γ微管蛋白是存于中心体的另一种微管蛋白, γ微管蛋白对微管的形成具有重要作用。
瑞典兰德大学的研究人员最近发现,RB1及γ微管蛋白通过结合到它们各自的基因启动子上,削弱了彼此的表达。
而且,同时减少RB1及γ微管蛋白水平,会导致E2F1依赖的凋亡基因(比如caspase 3)的上调。
研究发现,在不同的肿瘤类型,在RB1及γ微管蛋白的表达水平有一个负相关关系。在RB1无功能的肿瘤细胞系,γ微管蛋白的减少会导致凋亡的诱导。
因此,RB1/γ微管蛋白信号网络能够成为一个新的癌症治疗靶点。相关论文发表在4月6日的The Journal of Biological Chemistry。(生物谷Deepblue编译)
doi: 10.1074/jbc.M112.357038
PMC:
PMID:
Tumors with non-functional RB1 are killed by reduced gamma-tubulin levels
Asa Ehlen, Catalina A. Rossello, Kristoffer von Stedingk, Greta Hoog, Elise Nilsson, Helen M. Pettersson, Karin Jirstrom and Maria Alvarado-Kristensson.
In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway.Here, we describe that RB1 and γ tubulin proteins moderate each other's expression by binding to their respective gene promoters.Simultaneous reduction of RB1 and γ tubulin protein levels result in an E2F1-dependent upregulation of apoptotic genes such as caspase 3.We report that in various tumors types, there is an inverse correlation between the expression levels of γ tubulin and RB1 and that in tumor cell lines with a non-functioning RB1, reduction of γ tubulin protein levels leads to induction of apoptosis.Thus, the RB1/γ tubulin signal network can be considered as a new target for cancer treatment.