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

The levels of S100 Ca2+-binding proteins correlate with the progression of certain tumors, but their role, if any, in carcinogenesis is still poorly u nderstood. S100B protein associates with both the p53 oligomerization domai n (residues 325-355) and the extreme C terminus of the tumor suppressor p53 (residues 367-392). Consequently, S100B inhibits p53 tetramer formation an d 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 an d transcriptional activity. The effect of S100B is reflected in vivo by a r educed 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 requ ire p53 extreme C-terminal end to inhibit p53 activity. Collectively, these findings imply that elevated levels of S100B in tumors such as astrocytoma s and gliomas could inhibit p53 functions and contribute to cancer progress ion.