MED19

Official Full Name

mediator complex subunit 19

Organism

Homo sapiens

GeneID

219541

Background

The protein encoded by this gene is a subunit of the Mediator complex, which binds to gene-specific regulatory factors and provides support for the basal RNA polymerase II transcription machinery. This gene has been implicated in the growth of several types of cancer, and inhibition of its expression inhibits the growth and spread of these cancers. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

Synonyms

LCMR1; DT2P1G7; MED19AS;

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Detailed Information

The Med19 gene encodes a protein that is homologous to Mediator 19 (Med19), which promotes transcription in yeast, and is a subunit of the mediator (Med). The former name of Medl9 in yeast is ROX3 (or SSN7, RMR1, etc.), and in humans is lung cancer metastasis-related protein l (LCMR1).

Med19 is a component of the yeast and mammalian mediator complex head. Studies have found that after removal of the Med19 subunit, under certain conditions, the separation of the central component is caused, leaving a complete Med subcomplex consisting of the head and tail components, which indicates that Med19 has no effect on the joint head and tail components. , but can stabilize the position of the middle component in the Med. Studies have shown that simply removing the Med19 subunit and removing the entire central component distinguishes between transcriptional transcription and activation. Whether it is a simple deletion of Med19 or a deletion of the entire central component, the underlying transcription is reduced.

Figure 1. Model for the role of Med19 at the interface of Hox and MED. (Muriel Boube, et al.2014)

The Role of Med19

It was found that Med19/ Med16 plays an important role in the mediator silencing of neuronal genes induced by RE1 silencing transcription factor in the mediator complex. Med19/ Med16 is involved in specific gene suppression after neuronal maturation and REST (RE1 silencing transcription factor). An important link between REST-mediated neuronal maturation during early gene expression inhibition is required to be performed by RNA polymerase 2 transcriptional regulators. The mutation of Med19 causes defects in gene expression induced by Gal4 and Gcn4, and can also depress heat shock, sugar suppression, and H0 gene. Mammalian Med19 plays an important role in regulating gene expression, such as Med19, which binds directly to the RE1 transcriptional silencer and inhibits the expression of neural-related genes in non-neuronal cells. At present, the Med19 gene in humans has been defined as a tumor-associated gene, and Med19 has been found to be involved in the proliferation, metastasis and cycle regulation of various malignant tumors.

Med19 and Tumor

Electron expression profiling of LCMR1 using GenBank's UniGene database revealed that the gene is distributed in a variety of tumors and normal tissues, such as: carcinoid, sperm cell carcinoma, alveolar macrophages, lung epithelial cells, islet cell carcinoma, breast, heart, etc.

The siRNA-Med19 lentiviral expression vector was constructed and used to silence the Med19 gene in lung cancer cells by RNAi technology, which can induce tumor cell apoptosis and inhibit tumor cell growth. The results of RT-PCR and Western blotting confirmed that siRNA- Med19 was successfully Inhibition of Medl9 mRNA and protein expression in human lung cancer A549 cells. The shRNA lentiviral vector was used to infect the gastric cancer MGC-803 cells to silence the Med19 gene. The role of Med19 gene in the proliferation of gastric cancer cells was observed by MTT and clone formation experiments, and the effect of inhibiting the cell cycle of Med19 gene was confirmed by flow cytometry. As a result, the constructed shRNA lentiviral vector infects MGC-803 cells, and the cell proliferation ability is significantly decreased, and the cell clone formation ability is significantly weakened. At the same time, the cell cycle is arrested in the G1 phase, suggesting that Med19 plays an important role in tumor formation.

References:

Schiano, C. , Casamassimi, A. , Vietri, M. T. , Rienzo, M. , & Napoli, C. . (2014). The roles of mediator complex in cardiovascular diseases. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1839(6), 444-451.
Zhang, X. , Fan, Y. , Liu, B. , Qi, X. , Guo, Z. , & Li, L. . (2016). Med19 promotes breast cancer cell proliferation by regulating cbfa2t3/heb expression. Breast Cancer, 24(3), 1-9.
Muriel Boube., Bruno Hudry., & David L. Cribbs. . (2014). Drosophila melanogaster hox transcription factors access the rna polymerase ii machinery through direct homeodomain binding to a conserved motif of mediator subunit med19. PLoS Genetics, 10(5), e1004303.

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