Identification of functional domains involved in BTG1 cell localization

Rodier, Anne; Rochard, Pierrick; Berthet, Cyril; Rouault, Jean‐Pierre; Casas, François; Daury, Laetitia; Busson, Muriel; Magaud, Jean Pierre; Wrutniak‐Cabello, Chantal; Cabello, Gérard

doi:10.1038/sj.onc.1204398

Cited by 26 publications

(28 citation statements)

References 38 publications

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“…The highly conserved B box of BTG1 induced significant nuclear localization of h-galactosidase; it was enhanced by the presence of the COOH-terminal moiety. Moreover, the NH 2 -terminal LxxLL motif of BTG1, which mediates interaction with members of the nuclear receptor superfamily, also favored nuclear localization (31). The domains of BTG2 required for directing nuclear localization are consistent with these observations; the conserved boxes B and C of BTG1 and BTG2 share 100% and 80% homology, respectively.…”

Section: Discussionsupporting

confidence: 73%

Loss of B-Cell Translocation Gene-2 in Estrogen Receptor–Positive Breast Carcinoma Is Associated with Tumor Grade and Overexpression of Cyclin D1 Protein

Kawakubo

Brachtel²,

Hayashida

et al. 2006

Cancer Research

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The B-cell translocation gene-2 (BTG2) is present in the nuclei of epithelial cells in many tissues, including the mammary gland where its expression is regulated during glandular proliferation and differentiation in pregnancy. In immortalized mammary epithelial cells and breast cancer cells, BTG2 protein localized predominantly to the nucleus and cytoplasm, respectively. The highly conserved domains (BTG boxes A, B, and C) were required for regulating localization, suppression of cyclin D1 and growth inhibitory function of BTG2. Expression analysis of BTG2 protein in human breast carcinoma (n = 148) revealed the loss of nuclear expression in 46% of tumors, whereas it was readily detectable in the nuclei of adjacent normal glands. Loss of nuclear BTG2 expression in estrogen receptor-A (ERA)-positive breast tumors correlated significantly with increased histologic grade and tumor size. Consistent with its ability to suppress cyclin D1 transcription, loss of nuclear BTG2 expression in ER-positive breast carcinomas showed a significant correlation with cyclin D1 protein overexpression, suggesting that loss of BTG2 may be a factor involved in deregulating cyclin D1 expression in human breast cancer. (Cancer Res 2006; 66(14): 7075-82)

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Section: Discussionsupporting

confidence: 73%

Loss of B-Cell Translocation Gene-2 in Estrogen Receptor–Positive Breast Carcinoma Is Associated with Tumor Grade and Overexpression of Cyclin D1 Protein

Kawakubo

Brachtel²,

Hayashida

et al. 2006

Cancer Research

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“…We also reported that BTG1 is submitted to cellular trafficking and that T3 increases the nuclear localization of the protein. Interestingly, whereas a BTG1 mutant located in the cytoplasm is devoid of any myogenic activity, a mutant displaying major nuclear localization increases myoblast withdrawal from the cell cycle and stimulates myoblast differentiation (Rodier et al, 2001). These data established that BTG1 exerts its myogenic influence at nuclear level, and is a T3 target involved in the control of myoblast differentiation by the hormone .…”

Section: Introductionmentioning

confidence: 65%

“…In addition, we provided evidence that BTG1, submitted to cell trafficking, exerts its myogenic activity at nuclear level (Rodier et al, 2001). These data led us to As the protein displayed two LxxLL motifs considered to be involved in the interaction of coactivators with nuclear receptors (Heery et al, 1997), we privileged the possibility that BTG1 could act as a coactivator of several transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation

et al. 2005

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The btg1 (B-cell translocation gene 1) gene coding sequence was isolated from a translocation break point in a case of B-cell chronic lymphocytic leukaemia. We have already shown that BTG1, considered as an antiproliferative protein, strongly stimulates myoblast differentiation. However, the mechanisms involved in this influence remained unknown. In cultured myoblasts, we found that BTG1 stimulates the transcriptional activity of nuclear receptors (T3 and all-trans retinoic acid receptors but not RXRa and PPARc), c-Jun and myogenic factors (CMD1, Myf5, myogenin). Immunoprecipitation experiments performed in cells or using in vitro-synthesized proteins and GST pull-down assays established that BTG1 directly interacts with T3 and all-trans retinoic acid receptors and with avian MyoD (CMD1). These interactions are mediated by the transactivation domain of each transcription factor and the A box and C-terminal part of BTG1. NCoR presence induces the ligand dependency of the interaction with nuclear receptors. Lastly, deletion of BTG1 interacting domains abrogates its ability to stimulate nuclear receptors and CMD1 activity, and its myogenic influence. In conclusion, BTG1 is a novel important coactivator involved in the regulation of myoblast differentiation. It not only stimulates the activity of myogenic factors, but also of nuclear receptors already known as positive myogenic regulators.

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“…The cyclin-dependent kinase p34cdc2, in complex with either cyclin E or cyclin A, was shown to phosphorylate BTG1 on serine 159, facilitating the interaction of BTG1 with the human carbon catabolite repressor protein -associative factor 1 (29). Phosphorylation promoted the nuclear localization of BTG1, blocking cellular proliferation and resulting in growth inhibition (29,30). In addition, the Forkhead transcription factor FoxO3a was shown to directly induce the btg1 promoter, up-regulating the expression of BTG1 and stimulating differentiation of erythroid cells (20).…”

Section: Discussionmentioning

confidence: 99%

B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells

Nahta

Yuan

Fiterman

et al. 2006

Molecular Cancer Therapeutics

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The antiapoptotic protein Bcl-2 is overexpressed in a majority of breast cancers, and is associated with a diminished apoptotic response and resistance to various antitumor agents. Bcl-2 inhibition is currently being explored as a possible strategy for sensitizing breast cancer cells to standard chemotherapeutic agents. Antisense Bcl-2 oligonucleotides represent one method for blocking the antiapoptotic effects of Bcl-2. In this study, we show that antisense Bcl-2 efficiently blocks Bcl-2 expression, resulting in the apoptosis of breast cancer cells. Antisense Bcl-2-mediated cytotoxicity was associated with the induction of the B cell translocation gene 1 (BTG1 ). Importantly, knockdown of BTG1 reduced antisense Bcl-2-mediated cytotoxicity in breast cancer cells. Furthermore, BTG1 expression seems to be negatively regulated by Bcl-2, and exogenous expression of BTG1 induced apoptosis. These results suggest that BTG1 is a Bcl-2-regulated mediator of apoptosis in breast cancer cells, and that its induction contributes to antisense Bcl-2-mediated cytotoxic effects. [Mol Cancer Ther 2006;5(6):1593 -601]

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Identification of functional domains involved in BTG1 cell localization

Cited by 26 publications

References 38 publications

Loss of B-Cell Translocation Gene-2 in Estrogen Receptor–Positive Breast Carcinoma Is Associated with Tumor Grade and Overexpression of Cyclin D1 Protein

Loss of B-Cell Translocation Gene-2 in Estrogen Receptor–Positive Breast Carcinoma Is Associated with Tumor Grade and Overexpression of Cyclin D1 Protein

Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation

B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells

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