Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators.
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.
Mesh Terms:
Blotting, Northern, Breast Neoplasms, DNA Primers, Down-Regulation, Female, Fetal Proteins, Fluorescent Antibody Technique, Glutathione Transferase, Humans, Immunoblotting, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Neoplasm Proteins, Neoplasms, Ductal, Lobular, and Medullary, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Peptide Fragments, Polymerase Chain Reaction, RNA, Messenger, Ribonucleoproteins, Small Nuclear, Saccharomyces cerevisiae, Subcellular Fractions, Tumor Cells, Cultured, Two-Hybrid System Techniques
Blotting, Northern, Breast Neoplasms, DNA Primers, Down-Regulation, Female, Fetal Proteins, Fluorescent Antibody Technique, Glutathione Transferase, Humans, Immunoblotting, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Neoplasm Proteins, Neoplasms, Ductal, Lobular, and Medullary, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Peptide Fragments, Polymerase Chain Reaction, RNA, Messenger, Ribonucleoproteins, Small Nuclear, Saccharomyces cerevisiae, Subcellular Fractions, Tumor Cells, Cultured, Two-Hybrid System Techniques
Oncogene
Date: Aug. 15, 2002
PubMed ID: 12165861
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