Herpes simplex virus transactivator VP16 discriminates between HCF-1 and a novel family member, HCF-2.
Herpes simplex virus infection is initiated by VP16, a viral transcription factor that activates the viral immediate-early (IE) genes. VP16 does not recognize the IE gene promoters directly but instead forms a multiprotein complex with Oct-1 and HCF-1, a ubiquitous nuclear protein required for progression through the G1 phase of the cell cycle. The functional significance of recruiting HCF-1 to the VP16-induced complex is not understood. Here we describe the identification of a second HCF-like protein, designated HCF-2. HCF-2 is smaller than HCF-1 but shares three regions of strong amino acid sequence homology, including the beta-propeller domain required for association with VP16. HCF-2 is expressed in many tissues, especially the testis, and shows a more dynamic pattern of subcellular localization than HCF-1. Although HCF-2 associates with VP16 and can support complex assembly with Oct-1 and DNA, it is significantly less efficient than HCF-1. A similar preference is shown by LZIP, a cellular counterpart of VP16. Analysis of chimeric proteins showed that differences between the fifth and sixth kelch repeats of the beta-propeller domains from HCF-1 and HCF-2 dictate this selectivity. These results reveal an unexpected level of specificity in the recruitment of HCF-1 to the VP16-induced complex, paralleling the preferential selection of Oct-1 rather than the closely related POU domain protein Oct-2. Implications for regulation of the viral life cycle are discussed.
Johnson
K M
KM
Department of Microbiology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA.
Mahajan
S S
SS
Wilson
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D051790:G-Box Binding Factors; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; C497692:HCFC1 protein, human; C118856:HCFC2 protein, human; C497693:Hcfc1 protein, mouse; D017405:Herpes Simplex Virus Protein Vmw65; D051863:Host Cell Factor C1; D011506:Proteins; D014157:Transcription Factors