Metastasis-Associated Protein 1 Interacts with NRIF3, an Estrogen-Inducible Nuclear Receptor Coregulator

Talukder, Amjad H.; Gururaj, Anupama E.; Mishra, Sandip K.; Vadlamudi, Ratna K.; Kumar, Rakesh

doi:10.1128/mcb.24.15.6581-6591.2004

Cited by 44 publications

(47 citation statements)

References 37 publications

(40 reference statements)

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“…Although MTA1 is a part of the NuRD complex and associated with HDACs, its precise function as a corepressor remained speculative until recently, when MTA1 was found to act as a repressor for ligand-induced estrogen receptor (ER) transactivation in breast cancer cells (12). Surprisingly, however, recent studies have implicated two coactivators of ER, MICoA and NRIF3, as MTA1-binding partners, giving support to the notion that coactivators and corepressors may coexist in the same complex (13,14). Furthermore, in a transgenic mouse model of MTA1 (15), up-regulation of cyclin D1 was observed, prompting the authors to speculate that MTA1 may not be a universal corepressor.…”

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confidence: 96%

MTA1, a transcriptional activator of breast cancer amplified sequence 3

Gururaj

Singh

Rayala

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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115

107

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Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor α (ERα), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERα and involved a functional ERE half-site in BCAS3 . Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase II complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells.

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confidence: 96%

MTA1, a transcriptional activator of breast cancer amplified sequence 3

Gururaj

Singh

Rayala

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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115

107

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“…MTA1 was found to directly interact with histone deacetylases and repress the estrogen receptor a-driven transcription by recruiting histone deacetylase to the estrogen response element-containing target gene chromatin in breast cancer cells (5). MTA1 also interacts with a number of binding proteins that modulate its corepressor proteins (6)(7)(8)(9). In addition, MTA1 acts as a coactivator of breast cancer-amplified sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers (10).…”

Section: Introductionmentioning

confidence: 99%

Metastasis-Associated Protein 1 Transgenic Mice: A New Model of Spontaneous B-Cell Lymphomas

Bagheri‐Yarmand¹,

Balasenthil²,

Gururaj³

et al. 2007

Cancer Research

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Metastasis-associated protein 1 (MTA1), a component of the nuclear remodeling complex and the founding homologue of the MTA family, has been implicated in metastasis, but definitive causative evidence in an animal model system is currently lacking. Here, we show that MTA1 overexpression in transgenic mice is accompanied by a high incidence of spontaneous B cell lymphomas including diffuse large B cell lymphomas (DLBCL). Lymphocytes and lymphoma cells from MTA1-TG mice are hyperproliferative. Lymphomas were transplantable and of clonal origin and were characterized by down-regulation of p27Kip1 as well as up-regulation of Bcl2 and cyclin D1. The significance of these murine studies was established by evidence showing a widespread up-regulation of MTA1 in DLBCL from humans. These findings reveal a previously unrecognized role for the MTA1 pathway in the development of spontaneous B cell lymphomas, and offer a potential therapeutic target in B cell lymphomas. These observations suggest that MTA1-TG mice represent a new model of spontaneous DLBCL associated with high tumor incidence and could be used for therapeutic intervention studies. [Cancer Res 2007;67(15):7062-7]

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“…6 Unexpectedly, later studies demonstrated that MTA1 could functionally interact with at least two coactivator proteins, raising the possibility that MTA1 behaves as a coactivator under specific conditions or that coactivator and corepressor proteins exist in the same complex. 7,8 To determine which of these possibilities was true, we recently conducted a study in which we showed that MTA1 could indeed behave as a bona fide coactivator protein in vivo. 1 This functional transition of MTA1 from a corepressor to a coactivator molecule appeared due to two main causes: the acetylation status of MTA1 and the DNA sequence of the target gene.…”

Section: Implication Of Mta1 Acetylation In the Cellmentioning

confidence: 99%