The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR.
BACKGROUND
The transcriptional activity of Nuclear hormone Receptors (NRs) is regulated by interaction with coactivator or corepressor proteins. Many of these cofactors have been shown to have a misregulated expression or to show a subcellular mislocalization in cancer cell lines or primary tumors. Therefore they can be factors involved in the process of oncogenesis.


RESULTS
We describe a novel NR coregulator, TACC1, which belongs to the Transforming Acidic Coiled Coil (TACC) family. The interaction of TACC1 with Thyroid Hormone Receptors (TR) and several other NRs has been shown in a yeast two-hybrid screen and confirmed by GST pulldown, colocalization and co-immunoprecipitation experiments. TACC1 interacts preferentially with unliganded NRs. In F9 cells, endogenous TACC1 localized in the chromatin-enriched fraction of the nucleus and interacted with Retinoid Acid Receptors (RARalpha) in the nucleus. TACC1 depletion in the cell led to decreased RARalpha and TRalpha ligand-dependent transcriptional activity and to delocalization of TR from the nucleus to the cytoplasm.


CONCLUSIONS
From these experimental studies we propose that TACC1 might be a scaffold protein building up a transcriptional complex around the NRs we studied. This function of TACC1 might account for its involvement in several forms of tumour development.
Guyot
Romain
R
Institut de Génomique Fonctionnelle de Lyon, Universitéde Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Vincent
Séverine
S
Bertin
Julie
J
Samarut
Jacques
J
Ravel-Chapuis
Patrick
P
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C120584:TACC1 protein, human; D037021:Thyroid Hormone Receptors alpha