Dear T N, Sanchez-Garcia I, Rabbitts T H
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1993 May 15;90(10):4431-5. doi: 10.1073/pnas.90.10.4431.
A translocation involving human chromosome 10, band q24, in a subset of T-cell acute leukemias disrupts a region surrounding the putative oncogene HOX11, which encodes a protein with a homeodomain. The HOX11 protein binds to a specific DNA sequence, it localizes to the cell nucleus, and it transactivates transcription of a reporter gene linked to a cis-regulatory element, suggesting that HOX11 functions in vivo as a positive transcription activator. PCR analysis shows that the HOX11 homeodomain is a member of a distinct class of homeodomains, representatives of which occur in murine and Drosophila genomes. These all contain a threonine residue in place of the more common isoleucine or valine in helix 3 of the homeodomain. HOX11 therefore appears to belong to a family of DNA-binding transactivators of transcription.
在一部分T细胞急性白血病中,涉及人类10号染色体q24带的易位破坏了假定癌基因HOX11周围的一个区域,HOX11编码一种带有同源结构域的蛋白质。HOX11蛋白与特定的DNA序列结合,定位于细胞核,并反式激活与顺式调控元件相连的报告基因的转录,这表明HOX11在体内作为一种正转录激活因子发挥作用。PCR分析表明,HOX11同源结构域是一类独特的同源结构域的成员,其代表序列存在于小鼠和果蝇基因组中。这些同源结构域在同源结构域的螺旋3中都含有一个苏氨酸残基,取代了更常见的异亮氨酸或缬氨酸。因此,HOX11似乎属于转录的DNA结合反式激活因子家族。