Oct-1 is posttranslationally modified and exhibits reduced capacity to bind cognate sites at late times after infection with herpes simplex virus 1.
In herpes simplex virus 1-infected cells, a high level of alpha gene expression requires the transactivation of the genes by a complex containing the viral alpha transinducing factor (alphaTIF) and two cellular proteins. The latter two, HCF-1 and octamer binding protein Oct-1, are transcriptional factors regulated in a cell cycle-dependent manner. alphaTIF is a protein made late in infection but packaged with the virion to transactivate viral genes in newly infected cells. In light of the accumulation of large amounts of alphaTIF, the absence of alpha gene expression late in infection suggested the possibility that one or more transcriptional factors required for alpha gene expression is modified late in infection. Here we report that Oct-1 is posttranscriptionally modified late in infection, that the modification is mediated by the virus but does not involve viral protein kinases or cdc2 kinase activated by the virus late in infection, and that the modified Oct-1 has a reduced affinity for its cognate DNA site. These results are consistent with the hypothesis that modification of Oct-1 transcriptional factor could account at least in part for the shutoff of alpha gene expression late in infection.
The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, Illinois 60637, USA.
Sunil J
SJ
Advani
Lizette O
LO
Durand
Ralph R
RR
Weichselbaum
Bernard
B
Roizman
D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics*; D051863:Host Cell Factor C1; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D050811:Octamer Transcription Factor-1; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D014764:Viral Proteins
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D017874:Immediate-Early Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D014157:Transcription Factors; D014764:Viral Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D004247:DNA; D011494:Protein Kinases; C082380:UL13 protein, Simplexvirus; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1; D015739:Nocodazole