The AF2 domain of the orphan nuclear receptor TEC is essential for the transcriptional activity of the oncogenic fusion protein EWS/TEC

Cancer Lett. 2002 Sep 8;183(1):87-94. doi: 10.1016/s0304-3835(02)00104-0.

Abstract

The EWS/TEC fusion protein encoded by the t(9:22) chromosomal translocation in human extraskeletal myxoid chondrosarcoma tumors is thought to participate in the tumoral process at least in part by deregulating the expression of specific target genes involved in the control of cell proliferation. In this work we show that the activation function-2 (AF2) domain of TEC is essential for the transcriptional activity of the EWS/TEC fusion protein. Significantly, deleting only the last 15 amino acids of the fusion protein, which contains 949 amino acids in its full form, results in a loss of over 70% of its transcriptional activity in transfected human chondrocyte cell lines. Point mutation analyses indicate that within the AF2 domain, amino acid residues I939, D940 and F943 all play a crucial role in the activity of EWS/TEC. Comparable results were obtained with the native TEC receptor. These results suggest that EWS/TEC interacts at least in part with the same transcriptional coactivators as the native TEC receptor, and that these coactivators may be involved in the tumoral process leading to human chondrosarcoma tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Bone Neoplasms / genetics
  • Chondrosarcoma / genetics
  • Chromosomes, Human, Pair 22
  • Chromosomes, Human, Pair 9
  • Cloning, Molecular
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*
  • Transfection
  • Translocation, Genetic

Substances

  • DNA-Binding Proteins
  • Heterogeneous-Nuclear Ribonucleoproteins
  • NR4A3 protein, human
  • Nerve Tissue Proteins
  • Nr4a3 protein, mouse
  • Nuclear Proteins
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Recombinant Fusion Proteins
  • Ribonucleoproteins