A 36-amino-acid region of CIITA is an effective inhibitor of CBP: novel mechanism of gamma interferon-mediated suppression of collagen alpha(2)(I) and other promoters.
The class II transactivator (CIITA) is induced by gamma interferon (IFN-gamma) and activates major histocompatibility complex class II; however, this report shows it suppresses other genes. An N-terminal 36 amino acids of CIITA mediates suppression of the collagen alpha(2)(I) promoter via binding to CREB-binding protein (CBP). Reconstitution of cells with CBP reverts this suppression. IFN-gamma is known to inhibit collagen gene expression; to test if CIITA mediates this gene suppression, a mutant cell line defective in CIITA induction but not in the activation of STAT1/JAK/IRF-1 is studied. IFN-gamma suppression of the collagen promoter and the endogenous gene is observed in the wild-type control but not in the mutant line. Suppression is restored when CIITA is introduced. Other targets of CIITA-mediated promoter suppression include interleukin 4, thymidine kinase, and cyclin D1.
Zhu
X S
XS
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Ting
J P
JP
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D019556:COS Cells; D050882:CREB-Binding Protein; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D007371:Interferon-gamma / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
D024042:Collagen Type I; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma; D003094:Collagen; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse