|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 7, 5323-5330, February 16, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Human major histocompatibility (MHC) class I
antigen expression is important in controlling the metastatic growth of
malignant tumors. Locus-specific down-regulation of MHC class I gene
expression is frequently observed in human tumors, leading to decreased
susceptibility to cytotoxic T-cell-mediated lysis. The mechanism of
this down-regulation is incompletely understood. Here, we describe the
identification of human CCAAT displacement protein
(CDP/cut) as a locus-specific repressor of HLA-B and C gene
expression. Transient and stable transfections in HeLa and K562 cells
demonstrated the presence of a repressor element 650 base pairs
upstream of the first exon of HLA-B7. A specific binding complex with
the HLA-B7 and Cw2 repressor elements was demonstrated by EMSA.
Formation of the EMSA complex was inhibited specifically with
polyclonal antiserum to human CDP/cut, demonstrating that
CDP/cut binds the HLA-B7 repressor element. The
corresponding region of the HLA-A2 promoter neither repressed HLA-A2
gene expression nor bound CDP/cut. Overexpression of
CDP/cut in cell lines deficient in CDP/cut
resulted in a nearly 4-fold repression of reporter constructs
containing the HLA-B7 repressor element but not the corresponding
region of the HLA-A2 promoter. Repression of HLA-B and C gene
expression by CDP/cut does not involve displacement of
NF-Y, nor is CDP/cut associated with the histone
deacetylase HDAC1 when bound to the HLA-B7 repressor element. To our
knowledge, these results identify CDP/cut as the first
example of a locus-specific repressor of MHC class I gene transcription
in human tumor cells.
Identification of CCAAT Displacement Protein
(CDP/cut) as a Locus-specific Repressor of Major
Histocompatibility Complex Gene Expression in Human Tumor
Cells*
§¶
,,, and§**§§
Massey Cancer Center and the Departments of
§ Internal Medicine, ¶ Biochemistry and Molecular
Biophysics, and §§ Human Genetics, Medical
College of Virginia at Virginia Commonwealth University, Richmond,
Virginia 23298 and the ** Institute of Human Genetics, University of
Minnesota, Minneapolis, Minnesota 55455
*
This work was supported in part by National Institutes of
Health Grant NIH RO1-CA45634 (to G. G.) and aided by American Cancer Society Grant IN-105, the Thomas F. Jeffress and Kate Miller Jeffress Memorial Trust, and the Medical Research Endowment Trust and the A. D. Williams Trust funds at Virginia Commonwealth University (to
S. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
804-828-9723; Fax: 804-828-8453; E-mail: ssnyder@hsc.vcu.edu.
Present address: Abbott Laboratories, Dept. 463, 100 Abbott
Park Rd., Abbott Park, IL 60064-3500.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Chen, A. Unterbrink, S. Kadapakkam, J. Dong, T. T. Gu, J. Dickson, H.-H. Chuang, and M. MacDougall Regulation of the Cell Type-specific Dentin Sialophosphoprotein Gene Expression in Mouse Odontoblasts by a Novel Transcription Repressor and an Activator CCAAT-binding Factor J. Biol. Chem., October 1, 2004; 279(40): 42182 - 42191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schrem, J. Klempnauer, and J. Borlak Liver-Enriched Transcription Factors in Liver Function and Development. Part II: the C/EBPs and D Site-Binding Protein in Cell Cycle Control, Carcinogenesis, Circadian Gene Regulation, Liver Regeneration, Apoptosis, and Liver-Specific Gene Regulation Pharmacol. Rev., June 1, 2004; 56(2): 291 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Johnson Locus-Specific Constitutive and Cytokine-Induced HLA Class I Gene Expression J. Immunol., February 15, 2003; 170(4): 1894 - 1902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Boudreau, E. H. H. M. Rings, G. P. Swain, A. M. Sinclair, E. R. Suh, D. G. Silberg, R. H. Scheuermann, and P. G. Traber A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP Mol. Cell. Biol., August 1, 2002; 22(15): 5467 - 5478. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |