title: 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.affiliation: From the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Kira G
authors.initials: KG
authors.lastname: Hartman
authors.forename: Michele I
authors.initials: MI
authors.lastname: Vitolo
authors.forename: Adam D
authors.initials: AD
authors.lastname: Pierce
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Fox
authors.forename: Paul
authors.initials: P
authors.lastname: Shapiro
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Martin
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wilder
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D003600:Cytosol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D013912:Threonine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium
keywords: Calcium; Calcium Binding Proteins; Cancer; ERK; MAP Kinases (MAPKs); Melanoma; RSK; S100 Proteins