An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP.
In herpes simplex virus, lytic replication is initiated by the viral transactivator VP16 acting with cellular cofactors Oct-1 and HCF-1. Although this activator complex has been studied in detail, the role of HCF-1 remains elusive. Here, we show that HCF-1 contains an activation domain (HCF-1(AD)) required for maximal transactivation by VP16 and its cellular counterpart LZIP. Expression of the VP16 cofactor p300 augments HCF-1(AD) activity, suggesting a mechanism of synergy. Infection of cells lacking the HCF-1(AD) leads to reduced viral immediate-early gene expression and lowered viral titers. These findings underscore the importance of HCF-1 to herpes simplex virus replication and VP16 transactivation.
Luciano
Randy L
RL
Department of Microbiology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Wilson
Angus C
AC
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D066298:In Vitro Techniques; D016350:Leucine Zippers; D008954:Models, Biological; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014779:Virus Replication
C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C497692:HCFC1 protein, human; D017405:Herpes Simplex Virus Protein Vmw65; D051863:Host Cell Factor C1; D021122:Protein Subunits; D011506:Proteins; D014157:Transcription Factors