Inhibition of p53 transcriptional activity by the S100B calcium-binding protein.
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.
Lin
J
J
Biochemistry and Molecular Biology Department, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
Blake
M
M
Tang
C
C
Zimmer
D
D
Rustandi
R R
RR
Weber
D J
DJ
Carrier
F
F
D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D009414:Nerve Growth Factors / Q000502:physiology*; D009687:Nuclear Proteins; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D011817:Rabbits; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology
C493956:CDKN1A protein, human; D002135:Calcium-Binding Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2