A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein - PubMed

A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein

C Jousset et al. EMBO J. 1997.

Abstract

TEL is a novel member of the ETS family of transcriptional regulators which is frequently involved in human leukemias as the result of specific chromosomal translocations. We show here by co-immunoprecipitation and GST chromatography analyses that TEL and TEL-derived fusion proteins form homotypic oligomers in vitro and in vivo. Deletion mutagenesis identifies the TEL oligomerization domain as a 65 amino acid region which is conserved in a subset of the ETS proteins including ETS-1, ETS-2, FLI-1, ERG-2 and GABP alpha in vertebrates and PNTP2, YAN and ELG in Drosophila. TEL-induced oligomerization is shown to be essential for the constitutive activation of the protein kinase activity and mitogenic properties of TEL-platelet derived growth factor receptor beta (PDGFR beta), a fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic leukemia harboring a t(5;12) chromosomal translocation. Swapping experiments in which the TEL oligomerization domain was exchanged by the homologous domains of representative vertebrate ETS proteins including ETS-1, ERG-2 and GABP alpha show that oligomerization is a specific property of the TEL amino-terminal conserved domain. These results indicate that the amino-terminal domain conserved in a subset of the ETS proteins has evolved to generate a specialized protein-protein interaction interface which is likely to be an important determinant of their specificity as transcriptional regulators.

Similar articles

• A model for gene evolution of the ets-1/ets-2 transcription factors based on structural and functional homologies.

  Albagli O, Soudant N, Ferreira E, Dhordain P, Dewitte F, Begue A, Flourens A, Stehelin D, Leprince D. Albagli O, et al. Oncogene. 1994 Nov;9(11):3259-71. Oncogene. 1994. PMID: 7936650

• Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11.

  Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A, Riegman P, Lekanne Deprez R, Zwarthoff E, Hagemeijer A, et al. Buijs A, et al. Oncogene. 1995 Apr 20;10(8):1511-9. Oncogene. 1995. PMID: 7731705

• The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.

  Salomon-Nguyen F, Della-Valle V, Mauchauffe M, Busson-Le Coniat M, Ghysdael J, Berger R, Bernard OA. Salomon-Nguyen F, et al. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6757-62. doi: 10.1073/pnas.120162297. Proc Natl Acad Sci U S A. 2000. PMID: 10829078 Free PMC article.

• Ets oncogene family.

  Dhulipal PD. Dhulipal PD. Indian J Exp Biol. 1997 Apr;35(4):315-22. Indian J Exp Biol. 1997. PMID: 9315229 Review.

• Regulation of Ets function by protein - protein interactions.

  Li R, Pei H, Watson DK. Li R, et al. Oncogene. 2000 Dec 18;19(55):6514-23. doi: 10.1038/sj.onc.1204035. Oncogene. 2000. PMID: 11175367 Review.

Cited by

• Modulation of TEL transcription activity by interaction with the ubiquitin-conjugating enzyme UBC9.

  Chakrabarti SR, Sood R, Ganguly S, Bohlander S, Shen Z, Nucifora G. Chakrabarti SR, et al. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7467-72. doi: 10.1073/pnas.96.13.7467. Proc Natl Acad Sci U S A. 1999. PMID: 10377438 Free PMC article.

• An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors.

  Seidel JJ, Graves BJ. Seidel JJ, et al. Genes Dev. 2002 Jan 1;16(1):127-37. doi: 10.1101/gad.950902. Genes Dev. 2002. PMID: 11782450 Free PMC article.

• Analysis of the SUMO2 Proteome during HSV-1 Infection.

  Sloan E, Tatham MH, Groslambert M, Glass M, Orr A, Hay RT, Everett RD. Sloan E, et al. PLoS Pathog. 2015 Jul 22;11(7):e1005059. doi: 10.1371/journal.ppat.1005059. eCollection 2015 Jul. PLoS Pathog. 2015. PMID: 26200910 Free PMC article.

• Implication of a multisubunit Ets-related transcription factor in synaptic expression of the nicotinic acetylcholine receptor.

  Schaeffer L, Duclert N, Huchet-Dymanus M, Changeux JP. Schaeffer L, et al. EMBO J. 1998 Jun 1;17(11):3078-90. doi: 10.1093/emboj/17.11.3078. EMBO J. 1998. PMID: 9606190 Free PMC article.

References

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Nature Publishing Group
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal