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Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines.
Cell Growth Differ. 2001 Jun; 12(6):327-35.CG

Abstract

Melanoma cells commonly express MHC class II molecules constitutively. This is a rare, or possibly unique, phenotype for a nonprofessional antigen-presenting cell, where MHC class II expression ordinarily occurs only after IFN-gamma treatment. Despite the fact that constitutive expression of MHC class II on melanoma cells has been observed for decades and that the regulation of the MHC class II genes is well understood for many different cell types, there is no data regarding the basis for constitutive MHC class II expression in melanoma cells. Here we report that MHC class II expression in melanoma cells can be traced to constitutive expression of the class II transactivator protein (CIITA), which mediates both IFN-gamma-inducible and -constitutive MHC class II expression in all other cell types. In addition, we determined that constitutive CIITA expression is the result of the activation of both the B cell-specific CIITA promoter III and the IFN-gamma-inducible CIITA promoter IV, the latter of which previously has never been known to function as a constitutive promoter in any cell type. The recently described B cell-related ARE-1 activity is important for promoter III activation in the melanoma cells. Constitutive promoter IV activation involves the IFN regulatory factor element (IRF-E), which binds members of the IRF family of proteins, although the major, IFN-gamma inducible member of this family, IRF-1, is not constitutively expressed in these cells. In cells with constitutively active promoter IV, the promoter IV IRF-E is most likely activated by IRF-2. The relevance of these results to the pathway of melanoma development is discussed.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, College of Medicine and Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11432807

Citation

Goodwin, B L., et al. "Varying Functions of Specific Major Histocompatibility Class II Transactivator Promoter III and IV Elements in Melanoma Cell Lines." Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, vol. 12, no. 6, 2001, pp. 327-35.
Goodwin BL, Xi H, Tejiram R, et al. Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines. Cell Growth Differ. 2001;12(6):327-35.
Goodwin, B. L., Xi, H., Tejiram, R., Eason, D. D., Ghosh, N., Wright, K. L., Nagarajan, U., Boss, J. M., & Blanck, G. (2001). Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines. Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, 12(6), 327-35.
Goodwin BL, et al. Varying Functions of Specific Major Histocompatibility Class II Transactivator Promoter III and IV Elements in Melanoma Cell Lines. Cell Growth Differ. 2001;12(6):327-35. PubMed PMID: 11432807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines. AU - Goodwin,B L, AU - Xi,H, AU - Tejiram,R, AU - Eason,D D, AU - Ghosh,N, AU - Wright,K L, AU - Nagarajan,U, AU - Boss,J M, AU - Blanck,G, PY - 2001/7/4/pubmed PY - 2001/9/21/medline PY - 2001/7/4/entrez SP - 327 EP - 35 JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research JO - Cell Growth Differ VL - 12 IS - 6 N2 - Melanoma cells commonly express MHC class II molecules constitutively. This is a rare, or possibly unique, phenotype for a nonprofessional antigen-presenting cell, where MHC class II expression ordinarily occurs only after IFN-gamma treatment. Despite the fact that constitutive expression of MHC class II on melanoma cells has been observed for decades and that the regulation of the MHC class II genes is well understood for many different cell types, there is no data regarding the basis for constitutive MHC class II expression in melanoma cells. Here we report that MHC class II expression in melanoma cells can be traced to constitutive expression of the class II transactivator protein (CIITA), which mediates both IFN-gamma-inducible and -constitutive MHC class II expression in all other cell types. In addition, we determined that constitutive CIITA expression is the result of the activation of both the B cell-specific CIITA promoter III and the IFN-gamma-inducible CIITA promoter IV, the latter of which previously has never been known to function as a constitutive promoter in any cell type. The recently described B cell-related ARE-1 activity is important for promoter III activation in the melanoma cells. Constitutive promoter IV activation involves the IFN regulatory factor element (IRF-E), which binds members of the IRF family of proteins, although the major, IFN-gamma inducible member of this family, IRF-1, is not constitutively expressed in these cells. In cells with constitutively active promoter IV, the promoter IV IRF-E is most likely activated by IRF-2. The relevance of these results to the pathway of melanoma development is discussed. SN - 1044-9523 UR - https://www.unboundmedicine.com/medline/citation/11432807/Varying_functions_of_specific_major_histocompatibility_class_II_transactivator_promoter_III_and_IV_elements_in_melanoma_cell_lines_ L2 - http://cgd.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11432807 DB - PRIME DP - Unbound Medicine ER -