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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
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-
) 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
2(I) promoter via binding to CREB-binding protein (CBP).
Reconstitution of cells with CBP reverts this suppression. IFN-
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-
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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