The TET family of proteins: functions and roles in disease - PubMed (original) (raw)

Review

The TET family of proteins: functions and roles in disease

Adelene Y Tan et al. J Mol Cell Biol. 2009 Dec.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Domain structure of TET and SARFH/Cabeza proteins. The activation domain (AD), RGG boxes, RBD, Cys2–Cys2 zinc finger (ZF) and sarcoma breakpoints (arrowheads) are depicted for TLS, EWS and TAF15. The RGG boxes, RBD and Cys2–Cys2 ZF are also depicted for SARFH/Cabeza, the D. melanogaster ortholog.

Figure 2

Figure 2

TET proteins are highly related. Amino acid similarity and identity compared over the whole protein and within the RBD for TLS, EWS and TAF15.

Figure 3

Figure 3

Structure of TLS–CHOP and EWS–FLI1 fusion proteins. TLS and EWS are as described in Figure 1. CHOP contains a DNA-binding domain (DBD) and a Leucine Zipper (LZ) domain. Translocation breakpoint occurs upstream of the CHOP initiation site; TLS–CHOP fusion protein contains amino acids derived from sequences in the 5′ UTR of CHOP (hatched region). FLI1 contains an activation domain (AD) and an ETS DBD.

References

    1. Alex D., Lee K.A. RGG-boxes of the EWS oncoprotein repress a range of transcriptional activation domains. Nucleic Acids Res. 2005;33:1323–1331. - PMC - PubMed
    1. Aman P. Fusion genes in solid tumors. Semin. Cancer Biol. 1999;9:303–318. - PubMed
    1. Andersson M.K., Stahlberg A., Arvidsson Y., Olofsson A., Semb H., Stenman G., Nilsson O., Aman P. The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol. 2008;9:37. - PMC - PubMed
    1. Araya N., Hirota K., Shimamoto Y., Miyagishi M., Yoshida E., Ishida J., Kaneko S., Kaneko M., Nakajima T., Fukamizu A. Cooperative interaction of EWS with CREB-binding protein selectively activates hepatocyte nuclear factor 4-mediated transcription. J. Biol. Chem. 2003;278:5427–5432. - PubMed
    1. Araya N., Hiraga H., Kako K., Arao Y., Kato S., Fukamizu A. Transcriptional down-regulation through nuclear exclusion of EWS methylated by PRMT1. Biochem. Biophys. Res. Commun. 2005;329:653–660. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources