Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B.

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TitleRecognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B.
Publication TypeJournal Article
Year of Publication2006
AuthorsWilder, PT, Lin, J, Bair, CL, Charpentier, TH, Yang, D, Liriano, M, Varney, KM, Lee, A, Oppenheim, AB, Adhya, S, Carrier, F, Weber, DJ
JournalBiochim Biophys Acta
Volume1763
Issue11
Pagination1284-97
Date Published2006 Nov
ISSN0006-3002
KeywordsAmino Acid Sequence, Calgranulin B, Humans, Molecular Sequence Data, Nuclear Proteins, Peptides, Phosphorylation, Protein Conformation, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, S100 Proteins, Serine, Threonine, Tumor Suppressor Protein p53
Abstract

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.

DOI10.1016/j.bbamcr.2006.08.024
Alternate JournalBiochim. Biophys. Acta
PubMed ID17010455
Grant ListCA 107331 / CA / NCI NIH HHS / United States
GM 58888 / GM / NIGMS NIH HHS / United States
S10 RR 10441 / RR / NCRR NIH HHS / United States
S10 RR 15741 / RR / NCRR NIH HHS / United States
S10 RR 16812 / RR / NCRR NIH HHS / United States