Metastasis-associated Protein 1/Histone Deacetylase 4-Nucleosome Remodeling and Deacetylase Complex Regulates Phosphatase and Tensin Homolog Gene Expression and Function

Reddy, Sirigiri Divijendra Natha; Pakala, Suresh B.; Molli, Poonam R.; Sahni, Neil; Karanam, Narasimha Kumar; Mudvari, Prakriti; Kumar, Rakesh

doi:10.1074/jbc.m112.348474

Cited by 33 publications

(22 citation statements)

References 50 publications

(33 reference statements)

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“…We speculate that MTA1 may recruit class II HDACs to the ERpro315 region occupied by TFAP2C. In this regard, MTA1 was shown previously to bind HDAC4 (43). Interestingly, HDAC4 and HDAC5 interacted with p300 in MCF-7 but not in MDA-MB-231 ( Supplementary Fig.…”

Section: Discussionmentioning

confidence: 68%

Differential Regulation of Estrogen Receptor α Expression in Breast Cancer Cells by Metastasis-Associated Protein 1

et al. 2014

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Metastasis-associated protein 1 (MTA1) is a component of the nucleosome remodeling and histone deacetylase (HDAC) complex, which plays an important role in progression of breast cancer. Although MTA1 is known as a repressor of the transactivation function of estrogen receptor a (ERa), its involvement in the epigenetic control of transcription of the ERa gene ESR1 has not been studied. Here, we show that silencing of MTA1 reduced the level of expression of ERa in ERa-positive cells but increased it in ERa-negative cells. In both MCF7 and MDA-MB-231, MTA1 was recruited to the region þ146 to þ461 bp downstream of the transcription start site of ESR1 (ERpro315). Proteomics analysis of the MTA1 complex that was pulled down by an oligonucleotide encoding ERpro315 revealed that the transcription factor AP-2g (TFAP2C) and the IFN-g-inducible protein 16 (IFI16) were components of the complex. Interestingly, in MCF7, TFAP2C activated the reporter encoding ERpro315 and the level of ERa mRNA. By contrast, in MDA-MB-231, IFI16 repressed the promoter activity and silencing of MTA1 increased expression of ERa. Importantly, class II HDACs are involved in the MTA1-mediated differential regulation of ERa. Finally, an MDA-MB-231-derived cell line that stably expressed shIFI16 or shMTA1 was more susceptible to tamoxifen-induced growth inhibition in in vitro and in vivo experiments. Taken together, our findings suggest that the MTA1-TFAP2C or the MTA1-IFI16 complex may contribute to the epigenetic regulation of ESR1 expression in breast cancer and may determine the chemosensitivity of tumors to tamoxifen therapy in patients with breast cancer. Cancer Res; 74(5); 1484-94. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 68%

Differential Regulation of Estrogen Receptor α Expression in Breast Cancer Cells by Metastasis-Associated Protein 1

et al. 2014

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“…Recent reports also identified MTA1-NuRD as a new HIC1 corepressor that targets the HiREs (HIC1 binding sites) in the promoters of Cyclin D1 [90], p57KIP2 [90], and EphA2 [91] in WI38 cells. In addition, MTA1 was also observed to be involved in the transcriptional repression of Six3 [29,92], p21 WAF1 [37], MMP-9 [93], RNF114A [94], SMAD7 [95], and PTEN [93] via NuRD.…”

Section: Mta1 As a Co-repressor Of Gene Transcription Through The Nurmentioning

confidence: 97%

Subcellular localization of MTA proteins in normal and cancer cells

Liu

Wang

Huang

et al. 2014

Cancer Metastasis Rev

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The subcellular localization of a protein is closely linked to and indicates its function. The metastatic tumor antigen (MTA) family has been under continuous investigation since its identification two decades ago. MTA1, MTA2, and MTA3 are the main members of the MTA family. MTA1, as the representative member of this family, has been shown to be widely expressed in both embryonic and adult tissues, as well as in normal and cancerous conditions, indicating that MTA1 has functions both in physiological and pathological contexts. MTA1 is expressed at a higher level in most cancers than in their normal tissue counterparts. Even in normal cells, MTA1 levels vary a great deal from tissue to tissue. Importantly, MTA1 shows a multiple localization pattern in the cell, as do MTA2 and MTA3. Different MTA components in different subcellular compartments may exert different molecular functions in the cell. Previous studies revealed that MTA1 and MTA2 are predominately localized to the nucleus, while MTA3 is observed in both the nucleus and cytoplasm. Recent studies have reported that MTA1 is located in the nucleus, cytoplasm, and the nuclear envelope. In the nucleus, MTA1 dynamically interacts with chromatin in a MTA1-K532 methylation-dependent manner, whereas cytoplasmic MTA1 binds to the microtubule skeleton. MTA1 also shows a dynamic distribution during the cell cycle. Further investigations are needed to identify the exact subcellular localizations of MTA proteins. We review the sub-cellular localization patterns of the MTA family members and give a comprehensive overview of their respective molecular activities in multiple contexts.

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“…MAT1 (Talukder et al, 2003); MICoA (Mishra et al, 2003); NRIF3 (Talukder et al, 2004); and LMO4 (Singh et al, 2005)] and via recruitment of distinct transacting factor complexes to the target genes (Kang et al, 2014). In addition to blocking ER-transactivation, MTA1 also inhibits the transcription of breast cancer type 1 susceptibility gene (Molli et al, 2008), PTEN (Reddy et al, 2012), p21 WAF1 (Li and Kumar, 2010), guanine nucleotide-binding protein G(i) subunit alpha-2 (Ohshiro et al, 2010), SMAD family member 7 (SMAD7) (Salot and Gude, 2013), nuclear receptor subfamily 4 group A member 1 (Yu et al, 2013), and homeobox protein SIX3 (Manavathi et al, 2007), and represses BCL11B during T-cell leukemia (Cismasiu et al, 2005). …”

Section: Targets Of Mta Proteinsmentioning

confidence: 99%

Structure, expression and functions of MTA genes

Kumar

Wang

2016

Gene

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Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.

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Metastasis-associated Protein 1/Histone Deacetylase 4-Nucleosome Remodeling and Deacetylase Complex Regulates Phosphatase and Tensin Homolog Gene Expression and Function

Cited by 33 publications

References 50 publications

Differential Regulation of Estrogen Receptor α Expression in Breast Cancer Cells by Metastasis-Associated Protein 1

Differential Regulation of Estrogen Receptor α Expression in Breast Cancer Cells by Metastasis-Associated Protein 1

Subcellular localization of MTA proteins in normal and cancer cells

Structure, expression and functions of MTA genes

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