Importance of acidic, proline/serine/threonine-rich, and GTPbinding regions in the major histocompatibility complex class II transactivator: Generation of transdominant-negative mutants
- 18 March 1997
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 94 (6) , 2501-2506
- https://doi.org/10.1073/pnas.94.6.2501
Abstract
The class II transactivator (CIITA) is a master transcription regulator of gene products involved in the exogenous antigen presentation pathway, including major histocompatibility complex (MHC) class II, invariant chain, and DM. An extensive analysis of the putative functional domains of CIITA is undertaken here to explore the action of CIITA. Antibodies to CIITA protein were produced to verify that these mutant proteins are expressed. Both acidic and proline/serine/threonine-rich domains are essential for class II MHC promoter activation. In addition, three guanine nucleotide-binding motifs are essential for CIITA activity. Of these mutants, two exhibited strong transdominant-negative functions. These two mutants provide a plausible approach to manipulate MHC class II expression and immune responses.Keywords
This publication has 65 references indexed in Scilit:
- REGULATION OF MHC CLASS II GENES: Lessons from a DiseaseAnnual Review of Immunology, 1996
- A role for activator-mediated TFIIB recruitment in diverse aspects of transcriptional regulationCurrent Biology, 1995
- Increased Recruitment of TATA-Binding Protein to the Promoter by Transcriptional Activation Domains in VivoScience, 1994
- Regulation of MHC Class II Expression by Interferon-γ Mediated by the Transactivator Gene CIITAScience, 1994
- YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes.The Journal of Experimental Medicine, 1994
- The role of activators in assembly of RNA polymerase II transcription complexesCurrent Opinion in Genetics & Development, 1994
- Sequences and Factors: A Guide to MHC Class-II TranscriptionAnnual Review of Immunology, 1992
- The GTPase superfamily: conserved structure and molecular mechanismNature, 1991
- Congenital immunodeficiencies associated with absence of HLA class II antigens on lymphocytes result from distinct mutations in trans-acting factorsHuman Immunology, 1989
- T cell tolerance by clonal elimination in the thymusCell, 1987