The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.

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 express...

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Autores principales:	Milad J Alasady, Alexander R Terry, Adam D Pierce, Michael C Cavalier, Catherine S Blaha, Kaylin A Adipietro, Paul T Wilder, David J Weber, Nissim Hay
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e8cdda96b274951af8b33b4ddfe5607
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spelling	oai:doaj.org-article:9e8cdda96b274951af8b33b4ddfe56072021-12-02T20:17:46ZThe calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.1932-620310.1371/journal.pone.0256238https://doaj.org/article/9e8cdda96b274951af8b33b4ddfe56072021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256238https://doaj.org/toc/1932-6203S100B 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.Milad J AlasadyAlexander R TerryAdam D PierceMichael C CavalierCatherine S BlahaKaylin A AdipietroPaul T WilderDavid J WeberNissim HayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256238 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Milad J Alasady Alexander R Terry Adam D Pierce Michael C Cavalier Catherine S Blaha Kaylin A Adipietro Paul T Wilder David J Weber Nissim Hay The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
description	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.
format	article
author	Milad J Alasady Alexander R Terry Adam D Pierce Michael C Cavalier Catherine S Blaha Kaylin A Adipietro Paul T Wilder David J Weber Nissim Hay
author_facet	Milad J Alasady Alexander R Terry Adam D Pierce Michael C Cavalier Catherine S Blaha Kaylin A Adipietro Paul T Wilder David J Weber Nissim Hay
author_sort	Milad J Alasady
title	The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
title_short	The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
title_full	The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
title_fullStr	The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
title_full_unstemmed	The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
title_sort	calcium-binding protein s100b reduces il6 production in malignant melanoma via inhibition of rsk cellular signaling.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9e8cdda96b274951af8b33b4ddfe5607
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The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.

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