Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B.
S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins. A consensus sequence for S100B target proteins was published as (K/R)(L/I)xWxxIL and matches a region in the actin capping protein CapZ (V.V. Ivanenkov, G.A. Jamieson, Jr., E. Gruenstein, R.V. Dimlich, Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ, J. Biol. Chem. 270 (1995) 14651-14658). Several additional S100B targets are known including p53, a nuclear Dbf2 related (NDR) kinase, the RAGE receptor, neuromodulin, protein kinase C, and others. Examining the binding sites of such targets and new protein sequence searches provided additional potential target proteins for S100B including Hdm2 and Hdm4, which were both found to bind S100B in a calcium-dependent manner. The interaction between S100B and the Hdm2 and/or the Hdm4 proteins may be important physiologically in light of evidence that like Hdm2, S100B also contributes to lowering protein levels of the tumor suppressor protein, p53. For the S100B-p53 interaction, it was found that phosphorylation of specific serine and/or threonine residues reduces the affinity of the S100B-p53 interaction by as much as an order of magnitude, and is important for protecting p53 from S100B-dependent down-regulation, a scenario that is similar to what is found for the Hdm2-p53 complex.
Wilder
Paul T
PT
Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA.
Lin
Jing
J
Bair
Catherine L
CL
Charpentier
Thomas H
TH
Yang
Dong
D
Liriano
Melissa
M
Varney
Kristen M
KM
Lee
Andrew
A
Oppenheim
Amos B
AB
Adhya
Sankar
S
Carrier
France
F
Weber
David J
DJ
D000595:Amino Acid Sequence; D040502:Calgranulin B / Q000737:chemistry* / Q000378:metabolism; D018797:Cell Cycle Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry*; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism
D040502:Calgranulin B; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D013912:Threonine; D012694:Serine; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2