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

Connections (3)

This publication is referenced by other Labnodes entities: