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Translocated in liposarcoma, Ewing's sarcoma and TATA-binding protein-associated factor 15 constitute an interesting and important family of proteins known as the TET proteins. The proteins function in several aspects of cell growth control, including multiple different steps in gene expression, and they are also found mutated in a number of specific diseases. For example, all contain domains for binding nucleic acids and have been shown to function in both RNA polymerase II-mediated transcription and pre-mRNA splicing, possibly connecting these two processes. Chromosomal translocations in human sarcomas result in a fusion of the amino terminus of these proteins, which contains a transcription activation domain, to the DNA-binding domain of a transcription factor. Although the fusion proteins have been characterized in a clinical environment, the function of the cognate full-length protein in normal cells is a more recent topic of study. The first part of this review will describe the TET proteins, followed by detailed descriptions of their multiple roles in cells. The final sections will examine changes that occur in gene regulation in cells expressing the fusion proteins. The clinical implications and treatment of sarcomas will not be addressed but have recently been reviewed.

The TET Family of Proteins: Functions and Roles in Disease