Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators

Oncogene. 2002 Aug 15;21(36):5619-30. doi: 10.1038/sj.onc.1205658.

Abstract

The three human TACC genes encode a family of proteins that are suspected to play a role in carcinogenesis. Their function is not precisely known; a Xenopus TACC protein called Maskin is involved in translational control, while the Drosophila D-TACC associates with microtubules and centrosomes. We have characterized the human TACC1 gene and its products. The TACC1 gene is located in region p12 of chromosome 8; its mRNA is ubiquitously expressed and encodes a protein with an apparent molecular mass of 125 kDa, which is cytoplasmic and mainly perinuclear. We show that TACC1 mRNA gene expression is down-regulated in various types of tumors. Using immunohistochemistry of tumor tissue-microarrays and sections, we confirm that the level of TACC1 protein is down-regulated in breast cancer. Finally, using the two-hybrid screen in yeast, GST pull-downs and co-immunoprecipitations, we identified two potential binding partners for TACC1, LSM7 and SmG. They constitute a conserved subfamily of Sm-like small proteins that associate with U6 snRNPs and play a role in several aspects of mRNA processing. We speculate that down-regulation of TACC1 may alter the control of mRNA homeostasis in polarized cells and participates in the oncogenic processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • DNA Primers / chemistry
  • Down-Regulation
  • Female
  • Fetal Proteins*
  • Fluorescent Antibody Technique
  • Glutathione Transferase / metabolism
  • Humans
  • Immunoblotting
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms, Ductal, Lobular, and Medullary / genetics*
  • Neoplasms, Ductal, Lobular, and Medullary / metabolism
  • Neoplasms, Ductal, Lobular, and Medullary / pathology
  • Nuclear Proteins*
  • Oligonucleotide Array Sequence Analysis
  • Peptide Fragments / immunology
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism*
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Saccharomyces cerevisiae
  • Subcellular Fractions
  • Tumor Cells, Cultured / cytology
  • Two-Hybrid System Techniques

Substances

  • DNA Primers
  • Fetal Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Peptide Fragments
  • RNA, Messenger
  • Ribonucleoproteins, Small Nuclear
  • TACC1 protein, human
  • Glutathione Transferase