Structure, expression and functions of MTA genes

Abstract

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.

Epigenetic Regulation by Agonist-Specific Aryl Hydrocarbon Receptor Recruitment of Metastasis-Associated Protein 2 Selectively Induces Stanniocalcin 2 Expression

“…The human MTA protein family is composed of three isoforms (MTA1, MTA2, and MTA3) as well as several splice variants (Kumar and Wang, 2016). The MTA proteins do not appear to exhibit enzymatic activity nor bind DNA directly, but domain analyses suggest that the MTA proteins are capable of interacting with a large number of proteins.…”

Bcl11 Transcription Factors Regulate Cortical Development and Function

“…Both proteins repress the expression of their target genes when in a complex with COUP-TF or the NuRD complex (Cismasiu et al, 2005). NuRD complex is a major ATP-dependent chromatin remodeling complex consisting of a range of subunits like the metastasisassociated genes (MTAs) allowing the transcriptional regulation of target genes by binding tissue specific transcription factors (Lai and Wade, 2011;Kumar and Wang, 2016). This was shown for the binding of the Bcl11b-NuRD complex to its target gene p57KIP2, a cyclin dependent kinase, involving co-binding of MTA2 and HDAC2 (Topark-Ngarm et al, 2006).…”

Targeting Human Retinoblastoma Binding Protein 4 (RBBP4) and 7 (RBBP7)

“…The conserved N-terminus consists of four domains, BAH (Bromo adjacent homology), ELM2 (EGL-27 and MTA1 homology), SANT (SWI, ADA2, N-CoR, TFIIIB-B) and the GATA-like zinc finger domains. The variable C-terminus, consists of a Srchomology 3 binding domain, an acidic region, and a bipartite nuclear localization sequence (NLS; two in case of MTA1 and 2, one in case of MTA3) (reviewed in 32 ). The expression of MTA1 in normal cells significantly varies from tissue to tissue, and is relatively higher in normal testis, brain, liver and kidney suggesting a role in these tissues (reviewed in 31,34 ).…”