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

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.
Authors	J Lin, M Blake, C Tang, D Zimmer, R R Rustandi, D J Weber, F Carrier
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 37 Pg. 35037-41 (Sep 14 2001) ISSN: 0021-9258 [Print] United States
PMID	11454863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	CDKN1A protein, human Calcium-Binding Proteins Cyclin-Dependent Kinase Inhibitor p21 Cyclins Nerve Growth Factors Nuclear Proteins Proto-Oncogene Proteins S100 Calcium Binding Protein beta Subunit S100 Proteins S100B protein, human Tumor Suppressor Protein p53 DNA MDM2 protein, human Proto-Oncogene Proteins c-mdm2
Topics	Animals Calcium-Binding Proteins (physiology) Cyclin-Dependent Kinase Inhibitor p21 Cyclins (metabolism) DNA (metabolism) Humans Nerve Growth Factors (physiology) Nuclear Proteins Phosphorylation Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-mdm2 Rabbits S100 Calcium Binding Protein beta Subunit S100 Proteins Transcription, Genetic Tumor Cells, Cultured Tumor Suppressor Protein p53 (antagonists & inhibitors, chemistry, physiology)

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