CCAAT displacement protein regulates nuclear factor-kappa beta-mediated chemokine transcription in melanoma cells.

Ueda Y, Su Y, Richmond A
Melanoma Res. 2007 17 (2): 91-103

PMID: 17496784 · PMCID: PMC2665270 · DOI:10.1097/CMR.0b013e3280a60888

Members of the nuclear factor-kappa beta (NF-kappaB) family maintain cellular homeostasis by enhancing the transcription of genes involved in inflammation, immune response, cell proliferation, and apoptosis. Melanoma tumor cells often express inflammatory mediators through enhanced activation of NF-kappaB. The NF-kappaB activation appears to result from the enhancer formation including NF-kappaB and lysine acetyl transferases such as p300, CREB (cyclic AMP-responsive element binding protein)-binding protein (CBP), and/or p300/CBP associating factor (PCAF). We observed that proteins expressed by Hs294T metastatic melanoma cells are highly acetylated compared with normal melanocytes, and dominant-negative PCAF reduced the basal and tumor necrosis factor-alpha-stimulated transcriptional activity of NF-kappaB. The promoter activity of NF-kappaB-regulated chemokines was also reduced by the expression of dominant-negative PCAF. The promoters of these chemokines contain a CCAAT displacement protein (CDP)-binding site near the NF-kappaB element. compared with vector-transduced cells, in CDP-transduced Hs294T cells: (i) over-expressed CDP bound efficiently to PCAF, (ii) tumor necrosis factor-alpha-stimulated chemokine expression and NF-kappaB-mediated transcription were reduced, and (iii) the binding of CBP to Rel A was reduced. These data suggest that CDP inhibits cytokine-induced NF-kappaB-regulated chemokine transcription. This study contributes to our understanding of the role of CDP in an enhanceosome of NF-kappaB-mediated chemokine transcription in human melanoma cells.

MeSH Terms (20)

Apoptosis Cell Cycle Proteins Cell Line Cell Line, Tumor Chemokines Gene Expression Regulation, Neoplastic Histone Acetyltransferases Homeodomain Proteins Humans Melanoma Neoplasm Metastasis NF-kappa B Nuclear Proteins p300-CBP Transcription Factors Promoter Regions, Genetic Receptors, Interleukin-8A Receptors, Interleukin-8B Repressor Proteins Transcription, Genetic Transcription Factors

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