MTA1

Description

The MTA1 (metastasis associated 1) is a protein-coding gene located on chromosome 14.

Metastasis-associated protein MTA1 is a protein that in humans is encoded by the MTA1 gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments. MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex (NuRD). MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity. MTA1 participates in physiological functions in the normal and cancer cells. MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients.

== Discovery == MTA1 was first cloned by Toh, Pencil and Nicholson in 1994 as a differentially expressed gene in a highly metastatic rat breast cancer cell line. The role in MTA1 in chromatin remodeling was deduced due to the presence of MTA1 polypeptides in the NuRD complex. The first direct target of the MTA1-NuRD complex was ERα.

MTA1 is a transcriptional coregulator that can act as both a transcriptional corepressor and coactivator. It is a component of the histone deacetylase NuRD complex, which participates in chromatin remodeling. MTA1 regulates transcription by modifying the acetylation status of target chromatin and cofactor accessibility to target DNA. It acts as a transcriptional corepressor of BRCA1, ESR1, TFF1, and CDKN1A, and as a transcriptional coactivator of BCAS3 and SUMO2, independent of the NuRD complex. MTA1 stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. It regulates p53-dependent and -independent DNA repair processes following genotoxic stress, and regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2. MTA1 plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light. It positively regulates the CLOCK-BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. It regulates deacetylation of BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression. With TFCP2L1, MTA1 promotes the establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation.

MTA1 is also known as -.

Associated Diseases

WES Whole Exome Sequencing