Sapountzi Vasileia, Logan Ian R, Robson Craig N
Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Framlington Place, University of Newcastle Upon Tyne, Newcastle Upon Tyne NE2 4HH, United Kingdom.
Int J Biochem Cell Biol. 2006;38(9):1496-509. doi: 10.1016/j.biocel.2006.03.003. Epub 2006 Mar 28.
TIP60 was originally identified as a cellular acetyltransferase protein that interacts with HIV-1 Tat. As a consequence, the role of TIP60 in transcriptional regulation has been investigated intensively. Recent data suggest that TIP60 has more divergent functions than originally thought and roles for TIP60 in many processes, such as cellular signalling, DNA damage repair, cell cycle and checkpoint control and apoptosis are emerging. TIP60 is a tightly regulated transcriptional coregulator, acting in a large multiprotein complex for a range of transcription factors including androgen receptor, Myc, STAT3, NF-kappaB, E2F1 and p53. This usually involves recruitment of TIP60 acetyltransferase activities to chromatin. Additionally, in response to DNA double strand breaks, TIP60 is recruited to DNA lesions where it participates both in the initial as well as the final stages of repair. Here, we describe how TIP60 is a multifunctional enzyme involved in multiple nuclear transactions.
TIP60最初被鉴定为一种与HIV-1反式激活因子相互作用的细胞乙酰转移酶蛋白。因此,人们对TIP60在转录调控中的作用进行了深入研究。最近的数据表明,TIP60的功能比最初认为的更加多样化,并且TIP60在许多过程中的作用正在显现,如细胞信号传导、DNA损伤修复、细胞周期和关卡控制以及细胞凋亡。TIP60是一种受到严格调控的转录共调节因子,在一个大型多蛋白复合物中作用于一系列转录因子,包括雄激素受体、Myc、信号转导和转录激活因子3(STAT3)、核因子κB(NF-κB)、E2F1和p53。这通常涉及将TIP60乙酰转移酶活性募集到染色质上。此外,响应DNA双链断裂时,TIP60被募集到DNA损伤部位,在那里它参与修复的初始阶段和最终阶段。在此,我们描述了TIP60是如何成为一种参与多种核事务的多功能酶的。