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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,
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.

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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