GTP-dependent recruitment of CIITA to the class II major histocompatibility complex promoter.
We previously established that the class II transactivator CIITA binds GTP and disruption of the GTP binding ability of CIITA results in increased cytoplasmic CIITA, loss of nuclear CIITA, and thus diminished class II major histocompatibility complex transcription. Because of its role in facilitating nuclear localization, whether GTP binding is also required for CIITA-mediated transactivation of major histocompatibility class II genes remains unclear. We now show that recruitment of CIITA to the human leukocyte antigen (HLA)-DR promoter and activation of HLA-DR transcription is also GTP-dependent. After restoration of nuclear expression, CIITA mutants defective in GTP binding lack full transcriptional activation capacity. Although the availability of the activation domain of CIITA is unaltered, GTP mutants no longer cooperate with CREB-binding protein, p300, and pCAF and are defective in recruitment to the HLA-DR promoter.
Bewry
Nadine N
NN
Department of Molecular Medicine, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612, USA.
Bolick
Sophia C E
SC
Wright
Kenneth L
KL
Harton
Jonathan A
JA
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D019556:COS Cells; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D050882:CREB-Binding Protein; D006160:Guanosine Triphosphate; D006684:HLA-DR Antigens; D009687:Nuclear Proteins; D015534:Trans-Activators; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C083728:MHC class II transactivator protein