Stabilization but not the transcriptional activity of herpes simplex virus VP16-induced complexes is evolutionarily conserved among HCF family members.
The human herpes simplex virus (HSV) protein VP16 induces formation of a transcriptional regulatory complex with two cellular factors-the POU homeodomain transcription factor Oct-1 and the cell proliferation factor HCF-1-to activate viral immediate-early-gene transcription. Although the cellular role of Oct-1 in transcription is relatively well understood, the cellular role of HCF-1 in cell proliferation is enigmatic. HCF-1 and the related protein HCF-2 form an HCF protein family in humans that is related to a Caenorhabditis elegans homolog called CeHCF. In this study, we show that all three proteins can promote VP16-induced-complex formation, indicating that VP16 targets a highly conserved function of HCF proteins. The resulting VP16-induced complexes, however, display different transcriptional activities. In contrast to HCF-1 and CeHCF, HCF-2 fails to support VP16 activation of transcription effectively. These results suggest that, along with HCF-1, HCF-2 could have a role, albeit probably a different role, in HSV infection. CeHCF can mimic HCF-1 for both association with viral and cellular proteins and transcriptional activation, suggesting that the function(s) of HCF-1 targeted by VP16 has been highly conserved throughout metazoan evolution.
Lee
S
S
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Herr
W
W
D000818:Animals; D019556:COS Cells; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002455:Cell Division; D017362:Cyclic AMP Response Element-Binding Protein; D017405:Herpes Simplex Virus Protein Vmw65 / Q000737:chemistry / Q000502:physiology*; D051863:Host Cell Factor C1; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic
C107941:CREB3 protein, human; D029742:Caenorhabditis elegans Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C118856:HCFC2 protein, human; D017405:Herpes Simplex Virus Protein Vmw65; D051863:Host Cell Factor C1; D011506:Proteins; D014157:Transcription Factors