Retinoblastoma protein expression leads to reduced Oct-1 DNA binding activity and enhances interleukin-8 expression.
Tumor cell lines with a defective retinoblastoma gene are unable to transcribe the HLA class II genes in response to IFN-gamma treatment, and reconstitution of functional Rb rescues IFN-gamma-induced class II gene expression. However, the molecular mechanism of Rb rescue of the class II genes is unknown. We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA, the prototype class II gene. Oct-1, a POU domain transcription factor, was identified as a repressor of HLA-DRA promoter activity in the Rb-defective cells. Rb expression led to phosphorylation of Oct-1, thus relieving its repressive effect. Oct-1 has also been shown to repress interleukin 8 promoter activity. Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines, interleukin 8 expression is higher in these cell lines.
Zhang
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H
Department of Pathology and Laboratory Medicine, College of Medicine, University of South Florida, Tampa 33612, USA.
Shepherd
A T
AT
Eason
D D
DD
Wei
S
S
Diaz
J I
JI
Djeu
J Y
JY
Wu
G D
GD
Blanck
G
G
D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000378:metabolism; D059805:HLA-DR alpha-Chains; D051863:Host Cell Factor C1; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis*; D009504:Neutrophils / Q000502:physiology; D050811:Octamer Transcription Factor-1; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D051863:Host Cell Factor C1; D016209:Interleukin-8; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D016160:Retinoblastoma Protein; D014157:Transcription Factors