The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
PLoS One
; 16(8): e0256238, 2021.
Article
em En
| MEDLINE
| ID: mdl-34411141
S100B 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
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Proteínas Quinases S6 Ribossômicas 90-kDa
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Fator de Transcrição STAT3
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Subunidade beta da Proteína Ligante de Cálcio S100
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Melanoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article