Fusion Protein of Retinoic Acid Receptor α with Promyelocytic Leukemia Protein or Promyelocytic Leukemia Zinc Finger Protein Recruits N-CoR-TBLR1 Corepressor Complex to Repress Transcription in Vivo

Tomita, Akihiro; Buchholz, Daniel R.; Obata, Keiko; Shi, Yun

doi:10.1074/jbc.m303309200

Cited by 42 publications

(45 citation statements)

References 58 publications

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“…Tadpole organs were crushed in lysis buffer (10 mM Tris-HCl [pH 7.5], 150 mM NaCl, 5 mM EDTA, 1% Triton X-100, complete mini EDTA-free protease inhibitor tablet [Roche], 1 mM dithiothreitol) and then forced through a syringe after an equal volume of 2ϫ sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) loading buffer was added. The protein lysate was boiled, run on an SDS-PAGE gel, and subjected to anti-N-CoR and anti-FLAG (Stratagene) Western blotting (52,53). RNA from tails and intestines was isolated with TRIzol reagent (Invitrogen).…”

Section: Molecular Cloningmentioning

confidence: 99%

“…Assays were performed in triplicate. Western blotting, immunoprecipitation, and chromatin immunoprecipitation (ChIP) from oocytes were performed as previously described (52,53). Histology and TUNEL assay.…”

Section: Molecular Cloningmentioning

confidence: 99%

“…Oocytes were prepared according to established procedures (52,58). Wild-type and mutant TR and retinoid X receptor (RXR) mRNAs for oocyte injections were synthesized with mMESSAGE mMACHINE (Ambion) from the mutant TR templates (the present study) and pSP64[poly(A)]-TR␣A and pSP64[poly(A)]-RXR (59).…”

Section: Molecular Cloningmentioning

confidence: 99%

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Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis

Buchholz

Tomita

et al. 2004

Molecular and Cellular Biology

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120

108

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Thyroid hormone (T3) has long been known to be important for vertebrate development and adult organ function. Whereas thyroid hormone receptor (TR) knockout and transgenic studies of mice have implicated TR involvement in mammalian development, the underlying molecular bases for the resulting phenotypes remain to be determined in vivo, especially considering that T3 is known to have both genomic, i.e., through TRs, and nongenomic effects on cells. Amphibian metamorphosis is an excellent model for studying the role of TR in vertebrate development because of its total dependence on T3. Here we investigated the role of TR in metamorphosis by developing a dominant positive mutant thyroid hormone receptor (dpTR). In the frog oocyte transcription system, dpTR bound a T3-responsive promoter and activated the promoter independently of T3. Transgenic expression of dpTR under the control of a heat shock-inducible promoter in premetamorphic tadpoles led to precocious metamorphic transformations. Molecular analyses showed that dpTR induced metamorphosis by specifically binding to known T3 target genes, leading to increased local histone acetylation and gene activation, similar to T3-bound TR during natural metamorphosis. Our experiments indicated that the metamorphic role of T3 is through genomic action of the hormone, at least on the developmental parameters tested. They further provide the first example where TR is shown to mediate directly and sufficiently these developmental effects of T3 in individual organs by regulating target gene expression in these organs.

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Section: Molecular Cloningmentioning

confidence: 99%

Section: Molecular Cloningmentioning

confidence: 99%

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Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis

Buchholz

Tomita

et al. 2004

Molecular and Cellular Biology

Self Cite

120

108

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“…As an essential component of the SMRT (silencing mediator of retinoic acid and thyroid hormone receptors)/ N-CoR (nuclear receptor corepressor) nuclear receptor corepressor complex, TBL1XR1 plays a crucial role in regulating the activation of corepressors by modulating the ubiquitin status of SMRT/N-CoR complex (Zhang et al 2002;Tomita et al 2003Tomita et al , 2004Yoon et al 2003;Li and Wang 2008;Perissi et al 2008). In other words, TBL1XR1 can promote the transcription processes mediated by transcription factors, including NF-κB, nuclear receptors (NRs), Wnt/β-catenin and Notch pathways (Hoberg et al 2004;Choi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer

2017

Tohoku J. Exp. Med.

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Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the NCoR/SMRT transcription co-repressor complex, and its role in regulating cancer progression has been reported. Serous epithelial ovarian cancer (EOC) is the most common histological type of EOC. Here we explored the significance of TBL1XR1 expression in predicting outcomes of patients with serous EOC. Real-time quantitative PCR analysis showed that the expression level of TBL1XR1 mRNA was significantly higher in EOC tissues compared with adjacent non-tumorous tissues. The protein levels of TBL1XR1 in EOC tissues were assessed by immunohistochemistry, and the patients were classified into low-expression group (n = 62) and high-expression group (n = 54) according to the immunoreactivity. Prognostic significance of TBL1XR1 was evaluated by univariate and multivariate analyses, showing that over-expression of TBL1XR1 was correlated with poor prognosis. In addition, TBL1XR1 was positively associated with the lymph node metastasis of EOC. Because vascular endothelial growth factor (VEGF)-C is known as a critical mediator of lymph node metastasis, we measured the expression level of VEGF-C mRNA in EOC tissues and thus identified a positive correlation between TBL1XR1 and VEGF-C mRNA levels. Subsequently, using human EOC cell lines, we showed that silencing of TBL1XR1 decreased VEGF-C expression, suggesting that TBL1XR1 may function as an upstream regulator of VEGF-C in EOC. Furthermore, the proliferation and invasion of EOC cells were inhibited by TBL1XR1 silencing. In conclusion, TBL1XR1 overexpression may be an unfavorable prognostic factor for EOC. We also suggest that the TBL1XR1-VEGF-C axis may determine the EOC progression.

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“…Clinical treatment of PML-RAR acute promyelocytic leukemias with retinoic acid induces differentiation of leukemic blasts and disease remission, whereas PLZF-RAR acute promyelocytic leukemias are resistant to retinoic acid (60). Both RAR-a fusion proteins retain the ability to interact with NCoR and SMRT and recruit the nuclear hormone receptor corepressor-histone deacetylase-TBLR1 complex (61). This ability is critical for PML-RAR to be able to block the differentiation of hematopoietic precursor U937 cells.…”

Section: Corepressors and Cancermentioning

confidence: 99%

The Clinical Relevance of Steroid Hormone Receptor Corepressors

Kumar

Gururaj

Vadlamudi

et al. 2005

Clinical Cancer Research

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Steroid hormone receptors are ligand-dependent transcription factors that control a variety of essential physiologic and developmental processes in humans. The functional activity of a steroid receptor is regulated not only by hormones but also by an array of regulatory proteins such as coactivators, corepressors, and chromatin modifiers. Contrary to an earlier notion that corepressors and coactivators exist in separate complexes, these molecules, which have apparently opposite functions, are increasingly being found in the same complex, which allows for efficient transcriptional control mechanisms. These control mechanisms are in turn regulated by an array of post-translational modifications under the influence of upstream and local signaling networks. Because the outcome of steroidal hormone receptor transcriptional complexes is measured in terms of the expression of target genes, any dysregulation of coregulator complexes perturbs normal homeostasis and could contribute to the development and maintenance of malignant phenotypes. Increasing evidence implicating steroid hormone receptors and their coregulators in various pathophysiologic conditions has elicited interest in their structure and biology. Further advances in this field of study should open up a unique window for novel targeted therapies for diseases such as cancer. Here we briefly review the clinical relevance of corepressors, with a particular focus on their role in the development of cancerous phenotypes. Steroid hormone receptors (also known as nuclear receptors)are ligand-dependent transcription factors that control a variety of essential physiologic and developmental processes in humans (1 -3). Widely studied steroid hormone receptors include estrogen receptors, progesterone receptors, androgen receptors, and glucocorticoid receptors. The nuclear receptors primarily regulate the initiation of transcription by directly binding to specific DNA sequences in the regulatory region of target genes called hormone response elements and recruiting diverse ancillary factors characterized as coregulators along with the basal transcriptional machinery (4). For transcription factors to access DNA in the chromatin, the packaged chromatin structure needs to be partially unwound. The ligand-activated nuclear receptors are thought to mediate their transactivation functions by facilitating this regional loosening of the chromatin in the following manner. Ligand binding results in the dismissal of histone deacetylase -containing corepressor complexes and the concomitant recruitment of coactivator complexes. The coactivator complexes use their histone acetyltransferase activities to remodel the nucleosomal structures, thus opening up the chromatin and helping recruit the basal transcriptional machinery. In general, coregulators do not bind to DNA but are recruited to the target promoters via protein-protein interactions with the sequence-specific and context-dependent transcription factors (5). The relaxation and condensation of chromatin is tightly cont...

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Fusion Protein of Retinoic Acid Receptor α with Promyelocytic Leukemia Protein or Promyelocytic Leukemia Zinc Finger Protein Recruits N-CoR-TBLR1 Corepressor Complex to Repress Transcription in Vivo

Cited by 42 publications

References 58 publications

Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis

Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer

The Clinical Relevance of Steroid Hormone Receptor Corepressors

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