Complex formation between S100B protein and the p90 ribosomal S6 kinase (RSK) in malignant melanoma is calcium-dependent and inhibits extracellular signal-regulated kinase (ERK)-mediated phosphorylation of RSK.

Abstract	S100B is a prognostic marker for malignant melanoma. Increasing S100B levels are predictive of advancing disease stage, increased recurrence, and low overall survival in malignant melanoma patients. Using S100B overexpression and shRNA(S100B) knockdown studies in melanoma cell lines, elevated S100B was found to enhance cell viability and modulate MAPK signaling by binding directly to the p90 ribosomal S6 kinase (RSK). S100B-RSK complex formation was shown to be Ca(2+)-dependent and to block ERK-dependent phosphorylation of RSK, at Thr-573, in its C-terminal kinase domain. Additionally, the overexpression of S100B sequesters RSK into the cytosol and prevents it from acting on nuclear targets. Thus, elevated S100B contributes to abnormal ERK/RSK signaling and increased cell survival in malignant melanoma.
Authors	Kira G Hartman, Michele I Vitolo, Adam D Pierce, Jennifer M Fox, Paul Shapiro, Stuart S Martin, Paul T Wilder, David J Weber
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 18 Pg. 12886-95 (May 02 2014) ISSN: 1083-351X [Electronic] United States
PMID	24627490 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Multiprotein Complexes S100 Calcium Binding Protein beta Subunit S100B protein, human Threonine Ribosomal Protein S6 Kinases, 90-kDa Extracellular Signal-Regulated MAP Kinases Calcium
Topics	Blotting, Western Calcium (metabolism) Cell Line, Tumor Cell Nucleus (metabolism) Cell Survival (genetics) Cytosol (metabolism) Extracellular Signal-Regulated MAP Kinases (metabolism) Humans Melanoma (genetics, metabolism, pathology) Microscopy, Confocal Multiprotein Complexes (metabolism) Mutation Phosphorylation Protein Binding RNA Interference Ribosomal Protein S6 Kinases, 90-kDa (metabolism) S100 Calcium Binding Protein beta Subunit (genetics, metabolism) Threonine (metabolism)

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