Inhibition of p53 transcriptional activity by the S100B calcium-binding protein.

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TitleInhibition of p53 transcriptional activity by the S100B calcium-binding protein.
Publication TypeJournal Article
Year of Publication2001
AuthorsLin, J, Blake, M, Tang, C, Zimmer, DB, Rustandi, RR, Weber, DJ, Carrier, F
JournalJ Biol Chem
Volume276
Issue37
Pagination35037-41
Date Published2001 Sep 14
ISSN0021-9258
KeywordsAnimals, Calcium-Binding Proteins, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA, Humans, Nerve Growth Factors, Nuclear Proteins, Phosphorylation, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Rabbits, S100 Proteins, Transcription, Genetic, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Abstract

The levels of S100 Ca(2+)-binding proteins correlate with the progression of certain tumors, but their role, if any, in carcinogenesis is still poorly understood. S100B protein associates with both the p53 oligomerization domain (residues 325-355) and the extreme C terminus of the tumor suppressor p53 (residues 367-392). Consequently, S100B inhibits p53 tetramer formation and p53 phosphorylation mediated by protein kinase C, on p53 C-terminal end. In this report, we show that the S100B protein decreases p53 DNA binding and transcriptional activity. The effect of S100B is reflected in vivo by a reduced accumulation of p53, p21, and MDM2 protein levels in co-transfection assays and in response to bleomycin. The S100B can still interact with p53 in the absence of p53 extreme C-terminal end and reduce the expression of p53 downstream effector genes. These data indicate that S100B does not require p53 extreme C-terminal end to inhibit p53 activity. Collectively, these findings imply that elevated levels of S100B in tumors such as astrocytomas and gliomas could inhibit p53 functions and contribute to cancer progression.

DOI10.1074/jbc.M104379200
Alternate JournalJ. Biol. Chem.
PubMed ID11454863
Grant List1RO1GM57827-01 / GM / NIGMS NIH HHS / United States
R01GM58888 / GM / NIGMS NIH HHS / United States