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.
Conte
Nathalie
N
Département d'Oncologie Moléculaire, U119 Inserm, 27 Bd. Leï Roure, 13009, Marseille, France.
Charafe-Jauffret
Emmanuelle
E
Delaval
Bénédicte
B
Adélaïde
José
J
Ginestier
Christophe
C
Geneix
Jeannine
J
Isnardon
Daniel
D
Jacquemier
Jocelyne
J
Birnbaum
Daniel
D
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D005260:Female; D005326:Fetal Proteins; D005455:Fluorescent Antibody Technique; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured / Q000166:cytology; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; D005326:Fetal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D017411:Ribonucleoproteins, Small Nuclear; C120584:TACC1 protein, human; D005982:Glutathione Transferase