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Molecular and Cellular Biology, October 2001, p. 7078-7088, Vol. 21, No. 20
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.20.7078-7088.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen alpha 2(I) and Other Promoters

Xin-Sheng Zhu1,2 and Jenny P.-Y. Ting1,3,*

Lineberger Comprehensive Cancer Center,1 Curriculum in Oral Biology, School of Dentistry,2 and Department of Microbiology and Immunology,3 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295

Received 7 December 2000/Returned for modification 8 February 2001/Accepted 19 July 2001

The class II transactivator (CIITA) is induced by gamma interferon (IFN-gamma ) and activates major histocompatibility complex class II; however, this report shows it suppresses other genes. An N-terminal 36 amino acids of CIITA mediates suppression of the collagen alpha 2(I) promoter via binding to CREB-binding protein (CBP). Reconstitution of cells with CBP reverts this suppression. IFN-gamma is known to inhibit collagen gene expression; to test if CIITA mediates this gene suppression, a mutant cell line defective in CIITA induction but not in the activation of STAT1/JAK/IRF-1 is studied. IFN-gamma suppression of the collagen promoter and the endogenous gene is observed in the wild-type control but not in the mutant line. Suppression is restored when CIITA is introduced. Other targets of CIITA-mediated promoter suppression include interleukin 4, thymidine kinase, and cyclin D1.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, Campus Box 7295, Room 209, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-5538. Fax: (919) 966-8212. E-mail: panyun{at}med.unc.edu.

Molecular and Cellular Biology, October 2001, p. 7078-7088, Vol. 21, No. 20
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.20.7078-7088.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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