Constitutive and cytokine-induced expression of the melanoma growth stimulatory activity/GRO alpha gene requires both NF-kappa B and novel constitutive factors.

Wood LD, Richmond A
J Biol Chem. 1995 270 (51): 30619-26

PMID: 8530498 · DOI:10.1074/jbc.270.51.30619

Melanoma growth stimulatory activity (MGSA)/growth regulated (GRO) and interleukin-8 (IL-8) are highly related chemokines that have a causal role in melanoma progression. Expression of these chemokines is similar in that both require the NF-kappa B element and additional regions such as the CAAT/enhancer binding protein (C/EBP) element of the IL-8 promoter. The constitutive and cytokine IL-1-induced promoter activity of the chemokine MGSA/GRO alpha in normal retinal pigment epithelial and the Hs294T melanoma cells is partially regulated through the NF-kappa B element, which binds both NF-kappa B p50 and RelA (NF-kappa B p65) homodimers and heterodimers. Mutational analysis of the MGSA/GRO alpha promoter reveals that, in addition to the NF-kappa B element, the immediate upstream region (IUR) is necessary for basal expression in retinal pigment epithelial and Hs294T cells. Gel mobility shift and UV cross-linking analyses demonstrate that several constitutive DNA binding proteins interact with the IUR. Although this region has sequence similarity to the several transcription factor elements including C/EBP, the IUR includes sequences that have no similarity to previously identified enhancer regions. Furthermore, RelA transactivates through either the NF-kappa B element or the IUR, suggesting a putative interaction between NF-kappa B and this novel complex.

MeSH Terms (28)

Animals Base Sequence CCAAT-Enhancer-Binding Proteins Cell Line Chemokine CXCL1 Chemokines, CXC Chemotactic Factors Cross-Linking Reagents Cytokines DNA-Binding Proteins DNA Mutational Analysis Gene Expression Growth Inhibitors Growth Substances Humans Intercellular Signaling Peptides and Proteins Interleukin-8 Melanoma Molecular Sequence Data NF-kappa B Nuclear Proteins Pigment Epithelium of Eye Promoter Regions, Genetic Sequence Homology, Nucleic Acid Transcription Factor RelA Transcription Factors Tumor Cells, Cultured Ultraviolet Rays

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