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Molecular and Cellular Biology, August 2001, p. 4919-4928, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.4919-4928.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Self-Association of CIITA and Its Transactivation Potential

Tyler J. Sisk, Stacey Roys,dagger and Cheong-Hee Chang*

Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan 48109

Received 19 December 2000/Returned for modification 20 February 2001/Accepted 1 May 2001

The major histocompatibility complex (MHC) class II transactivator (CIITA) regulates the expression of genes involved in the immune response, including MHC class II genes and the interleukin-4 gene. Interactions between CIITA and sequence-specific, DNA-binding proteins are required for CIITA to function as an activator of MHC class II genes. CIITA also interacts with the coactivators CBP (also called p300), and this interaction leads to synergistic activation of MHC class II promoters. Here, we report that CIITA forms complexes with itself and that a central region, including the GTP-binding domain is sufficient for self-association. Additionally, this central region interacts with the C-terminal leucine-rich repeat as well as the N-terminal acidic domain. LXXLL motifs residing in the GTP-binding domain are essential for self-association. Finally, distinct differences exist among various CIITA mutant proteins with regard to activation function, subcellular localization, and association with wild-type protein and dominant-negative potential.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, The University of Michigan Medical School, 6606 Medical Sciences Building II, Ann Arbor, MI 48109-0620. Phone: (734) 647-7666. Fax: (734) 764-3562. E-mail: heechang{at}umich.edu.

dagger Present address: Department of Cardiovascular Science, Pfizer, Ann Arbor, MI 48105.


Molecular and Cellular Biology, August 2001, p. 4919-4928, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.4919-4928.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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