Involvement of CREB binding protein in expression of major histocompatibility complex class II genes via interaction with the class II transactivator.
The class II transactivator (CIITA) is a key regulatory factor that controls expression of the major histocompatibility complex (MHC) class II genes that are essential components for antigen presentation and thus regulation of the immune response. We show here that the adenovirus E1A protein interferes with the action of CIITA and inhibits both B-cell-specific and gamma interferon (IFN-gamma)-induced expression of MHC class II promoters. Transfection studies provide evidence for the functional role of the CREB-binding protein (CBP) in IFN-gamma and CIITA-mediated MHC class II promoter activation. We demonstrate that the N-terminally located transcription activation domain of CIITA physically interacts with both the N-terminal and the E1A-binding (C/H3) regions of CBP. These results suggest the involvement of a multisubunit complex, which contains the gene-specific coactivator CIITA and the versatile coactivator CBP, in MHC class II gene regulation, which may be responsible for both high-level expression and modulation by different signaling pathways.
Department of Biology, University of Crete, Heraklion, Crete, Greece.
A
A
Kretsovali
T
T
Agalioti
C
C
Spilianakis
E
E
Tzortzakaki
M
M
Merika
J
J
Papamatheakis
D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
D017500:Adenovirus E1A Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma