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

doi:10.1128/MCB.21.20.7078-7088.2001

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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 complexclass II; however, this report shows it suppresses other genes.An N-terminal 36 amino acids of CIITA mediates suppression ofthe 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 ifCIITA mediates this gene suppression, a mutant cell line defectivein CIITA induction but not in the activation of STAT1/JAK/IRF-1is studied. IFN- $gamma$ suppression of the collagen promoter and theendogenous gene is observed in the wild-type control but not inthe mutant line. Suppression is restored when CIITA is introduced.Other targets of CIITA-mediated promoter suppression include interleukin4, thymidine kinase, and cyclinD1.

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

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

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