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The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR.

ABSTRACT: 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.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.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.

SUBMITTER: Guyot R

PROVIDER: S-EPMC2822774 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR.

Guyot Romain R Vincent Séverine S Bertin Julie J Samarut Jacques J Ravel-Chapuis Patrick P

BMC molecular biology 20100115

<h4>Background</h4>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.<h4>Results</h4>We describe a novel NR coregulator, TACC1, which belongs to the Transforming Acidic Coiled Coil (TACC) fami ...[more]

PMID: 20078863

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Project description:BackgroundEndocervical adenocarcinoma (ECA) is further classified as human papillomavirus (HPV)-associated (HPVA) or non-HPVA (NHPVA), per the International Endocervical Adenocarcinoma Criteria and Classification (IECC). HPVA is a glandular tumor with stromal invasion and/or exophytic expansile-type invasion, associated with the typical molecular characteristics of high-risk HPV (HR-HPV) infection. Transforming acidic coiled-coil protein-3 (TACC3),an oncogene that is frequently abnormally expressed,represents a vital biomarker for multiple human malignancies. This study aimed to examine the role of TACC3 in the diagnosis and prognosis of ECA.MethodsWe analyzed 264 patients with ECA who underwent surgical resection, classifying their tumors into HPVA and NHPVA subtypes. The expression levels of TACC3, P16, MLH1, PMS2, MSH2, MSH6 and Ki-67 in tumors were evaluated by tissue microarray using immunohistochemistry (IHC). HPV subtypes were identified in formalin-fixed paraffin-embedded (FFPE) ECA tissues by the polymerase chain reaction (PCR).ResultsECA samples showed increased TACC3 expression relative to adjacent non-carcinoma samples. TACC3 expression was higher in HPVA than in NHPA. In the HPVA subtype, high TACC3 expression was significantly correlated with P16-positive, Ki-67-high expression. Furthermore, TACC3 levels were significantly related to tumor histological type (P = 0.006), nerve invasion (P = 0.003), differentiation (P = 0.004), surgical margin (P = 0.012), parametrium invasion (P = 0.040), P16 expression (P < 0.001), and Ki-67 (P = 0.004). Additionally, Kaplan-Meier analysis showed that TACC3 upregulation was associated with poor overall survival (OS, P = 0.001), disease-free survival (DFS, P < 0.001), and recurrence survival (P < 0.001). Multivariate analysis indicated that elevated TACC3 expression served as a marker to independently predict ECA prognosis. ROC curve analyses indicated that TACC3, P16, and HPV subtypes showed similar utility for distinguishing HPVA from NHPVA, with areas under the ROC curves of 0.640, 0.649, and 0.675, respectively. The combination of TACC3 and HPV subtypes improved the diagnostic performance of ECA compared with TACC3, P16, and HPV subtypes alone.ConclusionsTaken together, our findings identify that TACC3 is a promising complementary biomarker for diagnosis and prognosis for patients with ECA.

Dataset Information

The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR.

Publications

The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR.

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