HHR23A, the human homologue of the yeast repair protein RAD23, interacts specifically with Vpr protein and prevents cell cycle arrest but not the transcriptional effects of Vpr.
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.
Gragerov
A
A
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Kino
T
T
Ilyina-Gragerova
G
G
Chrousos
G P
GP
Pavlakis
G N
GN
D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D016336:Gene Products, vpr / Q000235:genetics*; D016334:Genes, vpr; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D014158:Transcription, Genetic; D014779:Virus Replication / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; C086985:RAD23A protein, human; D045643:DNA Repair Enzymes