title: Towards an understanding of the structure and function of MTA1.
abstract: Gene expression is controlled through the recruitment of large coregulator complexes to specific gene loci to regulate chromatin structure by modifying epigenetic marks on DNA and histones. Metastasis-associated protein 1 (MTA1) is an essential component of the nucleosome remodelling and deacetylase (NuRD) complex that acts as a scaffold protein to assemble enzymatic activity and nucleosome targeting proteins. MTA1 consists of four characterised domains, a number of interaction motifs, and regions that are predicted to be intrinsically disordered. The ELM2-SANT domain is one of the best-characterised regions of MTA1, which recruits histone deacetylase 1 (HDAC1) and activates the enzyme in the presence of inositol phosphate. MTA1 is highly upregulated in several types of aggressive tumours and is therefore a possible target for cancer therapy. In this review, we summarise the structure and function of the four domains of MTA1 and discuss the possible functions of less well-characterised regions of the protein.
authors.affiliation: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Millard
authors.forename: Louise
authors.initials: L
authors.lastname: Fairall
authors.forename: John W R
authors.initials: JW
authors.lastname: Schwabe
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1 / Q000235:genetics; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics*; D006657:Histones / Q000235:genetics; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D006657:Histones; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases