Contribution of transcription factors to oncogenesis.

Abstract

Transcription factors coordinate consitutive and inducible gene expression. They recognize and bind specific DNA sequences that are present in the regulatory regions of all genes, and thus allow transcriptional activation or repression of that given gene. Most transcription factors do not operate on their own, but form multiunit complexes consisting of homo- or heterodimers. A variety of genetic alterations observed in solid and hematologic malignancies result in gain or loss of function mutations of these molecules. As a consequence, a given transcription factor modulates its binding specificity and thus regulates the expression of a different set of target genes in the tumor cell as compared with normal cells. Alternatively, the transcription factor modulates its ability to interact with partner molecules and thus its binding specificity, its response to incoming signals or its functional activity, that is transcriptional activation or transcriptional repression of the targeted gene. Based on their functional implication in regulating gene expression and thus cellular behavior, loss or gain of function of transcription factor genes play a major role in the development or progression of tumors.