A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.

Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was ...
identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification.
Mesh Terms:
Binding Sites, Cell Line, Tumor, Cell Proliferation, Cytomegalovirus, Gene Expression Regulation, Neoplastic, Genes, Reporter, HEK293 Cells, Humans, Luciferases, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-mdm2, Signal Transduction, Transcription Factors, TFII, Transcription, Genetic, Tumor Suppressor Protein p53, beta-Galactosidase
PLoS ONE
Date: Dec. 15, 2015
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