The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling
AuthorAlasady, Milad J
Terry, Alexander R
Pierce, Adam D
Cavalier, Michael C
Blaha, Catherine S
Adipietro, Kaylin A
Wilder, Paul T
Weber, David J
PublisherPublic Library of Science
MetadataShow full item record
AbstractS100B is frequently elevated in malignant melanoma. A regulatory mechanism was uncovered here in which elevated S100B lowers mRNA and secreted protein levels of interleukin-6 (IL6) and inhibits an autocrine loop whereby IL6 activates STAT3 signaling. Our results showed that S100B affects IL6 expression transcriptionally. S100B was shown to form a calcium-dependent protein complex with the p90 ribosomal S6 kinase (RSK), which in turn sequesters RSK into the cytoplasm. Consistently, S100B inhibition was found to restore phosphorylation of a nuclear located RSK substrate, CREB, which is a potent transcription factor for IL6 expression. Thus, elevated S100B reduces IL6-STAT3 signaling via RSK signaling pathway in malignant melanoma. Indeed, the elevated S100B levels in malignant melanoma cell lines correspond to low levels of IL6 and p-STAT3.
Interleukin 6--antagonists & inhibitors
STAT3 Transcription Factor
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16490
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