Gragerov A, Kino T, Ilyina-Gragerova G, Chrousos G P, Pavlakis G N
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Virology. 1998 Jun 5;245(2):323-30. doi: 10.1006/viro.1998.9138.
Yeast two-hybrid selection of proteins interacting with human immunodeficiency virus type 1 Vpr identified HHR23A, a human homologue of the yeast DNA repair protein RAD23, as a specific interactor. A small 57-amino-acid C-terminal portion of HHR23A was sufficient for Vpr interaction. When introduced into human cells by transfection, full-length HHR23A or its C-terminal fragments were able to alleviate Vpr-induced cell cycle arrest, suggesting that HHR23A may participate in the pathway leading to G2 arrest by Vpr. We have also examined the effects of HHR23 on the recently identified transcription coactivator function of Vpr. The two Vpr functions are independent, since we have identified mutants lacking either the cell cycle arrest or the coactivator function. Our analysis showed that excess of HHR23A does not affect the coactivator function of Vpr, while it affects the cell cycle arresting function. Therefore, a simple sequestering model for Vpr in the presence of excess HHR23A is not supported. We propose that the interaction of HHR23A with Vpr may affect specifically pathways leading to cell cycle regulation.
通过酵母双杂交筛选与人类免疫缺陷病毒1型Vpr相互作用的蛋白质，鉴定出HHR23A，它是酵母DNA修复蛋白RAD23的人类同源物，为特异性相互作用分子。HHR23A一个含57个氨基酸的小C末端部分足以与Vpr相互作用。通过转染将全长HHR23A或其C末端片段导入人细胞时，它们能够缓解Vpr诱导的细胞周期停滞，这表明HHR23A可能参与Vpr导致G2期停滞的途径。我们还研究了HHR23对最近确定的Vpr转录共激活因子功能的影响。Vpr的这两种功能是独立的，因为我们鉴定出了缺乏细胞周期停滞功能或共激活因子功能的突变体。我们的分析表明，过量的HHR23A不影响Vpr的共激活因子功能，但会影响细胞周期停滞功能。因此，不支持在存在过量HHR23A时Vpr的简单隔离模型。我们提出，HHR23A与Vpr的相互作用可能特异性地影响导致细胞周期调控的途径。
