MEN1

Official Full Name

menin 1

Organism

Homo sapiens

GeneID

4221

Background

This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

Synonyms

MEAI; SCG2;

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Detailed Information

The multiple endocrine neoplasia ty pe 1 (MEN1) is a familial autosomal dominant disease characterized by endocrine organ tumors such as parathyroid glands, islets, and anterior pituitary tumors. It also named as Wermer syndrome. Its pathogenic key gene MEN1 is located on chromosome 11q13, and Menin protein is the expression product of MEN1 gene. The MEN1 gene expresses a variety of biological functions in the body, and is thus widely involved in the regulation of body metabolism.

Figure 1. Menin: a scaffold protein that controls gene expression and cell signaling.（Matkar, S. , et al. 2013）

MEN1 and cell Proliferation

Cell proliferation of mouse embryonic fibroblasts (MEF cells) knocked out by Men1 gene was significantly accelerated. Exogenous introduction of MEN1 gene inhibited cell proliferation; Men1 gene deletion or mutation significantly promoted islet cell proliferation. Molecular mechanism studies have found that Menin interacts with JunD, Pem, NF-κB, Smad-3, and ASK (activato r of sphase kinase), which regulate key cell proliferation, and negatively regulate cell proliferation. In the Men1 knockout mice, the islets were abnormally enlarged, and the loss of Men1 resulted in a decrease in the transcription level of p 27 Kip 1 in pancreatic cells. These results elucidate some of the mechanisms by which Menin inhibits beta cell proliferation and provide new insights into the treatment of MEN1 tumors by inhibiting the CDK2 pathway and by treating beta cell proliferation to treat type 1 diabetes.

MEN1 and Apoptosis

The study found that Menin plays an important role in the regulation of DNA damage repair and cell survival by interacting with the FANCD2 gene associated with congenital myelodysplasia. For example, gamma-ray irradiation enhances the Menin/FANCD2 interaction. Menin is concentrated in the chromatin and nuclear matrix regions, and the association with the nuclear matrix can be activated by gamma rays. It was found that Menin is involved in cisplatin-induced apoptosis in malignant melanoma cells, and some mechanisms are involved in the inhibition of γ-H2A X phosphorylation by Menin. Men1 knockout antagonized TNF-α-induced cell apoptosis, and Men1-/-M EF cells supplemented with Menin restored sensitivity to TNF-α. Menin indirectly affects apoptosis by regulating the expression of caspase8, which binds to the caspase 8 gene locus and up-regulates caspase8 expression, thereby enhancing cell sensitivity to TNF-α or radiation-induced apoptosis, but it has to little effect basic level of apoptosis. Two Menin mutants (L22R and A242V) derived from human MEN1 tumors have lost the transcriptional regulation of caspase8 mRNA, thereby resisting TNF-α-induced apoptosis. It suggested that Menin inhibits endocrine tumors at least in part by regulating the expression of caspase8.

MEN1 and Disease

MEN1 syndrome is an autosomal dominant disease characterized by familial parathyroid glands, islets, and anterior pituitary tumors, as well as tumors of adrenal cortical tumors, carcinoid tumors, lipomas, and pheochromocytoma. In these tumors, the level of Menin expression is reduced. The study found that the expression of Menin in the nucleus of the anterior pituitary of normal humans is high, while the expression of Menin in pituitary adenomas varies greatly. studies have also shown that TGF-β can inhibit the proliferation of pituitary tumor cells, but the inactivation of Menin antagonizes TGFβ Mediated inhibition of cell proliferation suggests that changes in the expression of Menin may be one of the causes of pituitary tumors.The mechanism by which the MEN1 gene contributes to tumor formation is mainly through the loss of function of the biallelic gene, which causes minor mutations such as missense mutations, or larger mutations such as loss of heterozygosity.

References:

Matkar, S. , Thiel, A. , & Hua, X. . (2013). Menin: a scaffold protein that controls gene expression and cell signaling. Trends in Biochemical Sciences, 38(8).
Gaztambide, S., Vazquez, F., & Castaã±O, L. (2013). Diagnosis and treatment of multiple endocrine neoplasia type 1 (men1). Minerva Endocrinologica, 38(1), 17-28.
Fang, M., Xia, F., Mahalingam, M., Virbasius, C. M., Wajapeyee, N., & Green, M. R. (2013). Men1 is a melanoma tumor suppressor that preserves genomic integrity by stimulating transcription of genes that promote homologous recombination-directed dna repair. Molecular & Cellular Biology, 33(13), 2635-2647.

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