摘要
p27Kip1作为细胞周期依赖性激酶抑制因子(CDKI),参与细胞周期的负向调控,在细胞的增殖、分化、凋亡和细胞间粘附等方面起重要作用。正常组织中p27Kip1高表达并主要存在于细胞核内,而肿瘤组织中p27Kip1低表达并集中在细胞核外分布,较少出现突变和甲基化。虽然翻译后调控的机制很多,但其错位分布和低表达的转录水平调控机制尚不清楚。近来研究发现,Sp1、CTF、E2F、NF-Y、NF-κB等众多转录因子以与p27Kip1启动子区的相应位点结合的不同的时间和空间为顺序,可能参与p27Kip1的表达和亚细胞分布的调控。本文综述了不同转录因子在p27Kip1启动子区结合的时空顺序对其转录的影响,有利于进一步阐明p27Kip1启动子区调控的分子机制,并为临床筛选相应的转录因子作为治疗靶点提供理论依据。
As a member of cyclin-dependent kinase inhibitors,p27Kip1could function as a negative regulator on cell cycle and play important roles on cell proliferation,differentiation,apoptosis and cell-cell adhesion.In normal cell,p27Kip1 is high expressed in nucleus,conversely,low expression mainly displaced into the cytoplasm of tumor cells.Although the post-translational regulation of p27^Kip1 is well established,much less is known about the molecular mechanisms of its abnormal expression and mislocalization,its transcriptional regulation is also largely unknown.Until recently,studies have shown that the binding of transcriptional factors,such as Sp1,NF-κB,especially with different interacting profiles,to the particular sequences of p27^Kip1promoter might regulate its expression and subcelluar distribution.To experimentally identify potential transcriptional factors mediating the function of p27^Kip1genes,here we review the transcriptional factors profile and their binding sites located in the promoter of p27^Kip1,which might contribute to illustrate the mechanism of p27^Kip1 promoter regulation and select the transcriptional factors as a novel therapy targeting for human cancer theoretically.
出处
《临床肿瘤学杂志》
CAS
2011年第2期170-173,共4页
Chinese Clinical Oncology
基金
国家自然科学基金资助项目(30870962
30470669)
