MGMT
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Official Full Name
O-6-methylguanine-DNA methyltransferase -
Overview
MGMT (O6 methylguanine DNA methyltransferase) is an enzyme that transfers methyl groups from O(6) methylguanine, and other methylated moities of DNA, to a cysteine residue in itself, thus repairing DNA damage caused by alkylation in a single step reaction. This is a suicide reaction as the enzyme is irreversibly inactivated. MGMT prevents mutagenesis and malignant transformation, and also provides resistance to chemotherapy with alkylating agents among cancer patients. -
Synonyms
MGMT;O-6-methylguanine-DNA methyltransferase;methylated-DNA--protein-cysteine methyltransferase;methylguanine-DNA methyltransferase;O-6-methylguanine-DNA-alkyltransferase;O6-methylguanine-DNA methyltransferase;6-O-methylguanine-DNA methyltransferase
Recombinant Proteins
- Human
- Rat
- Rhesus macaque
- Zebrafish
- Mouse
- E.coli
- Mammalian Cells
- Sf9 Cells
- HEK293
- Wheat Germ
- In Vitro Cell Free System
- His
- GST&His
- T7
- Non
- His&Strep
- DDK&Myc
- Flag
- Avi&Fc&His
- GST
Background
What is MGMT protein?
MGMT (O-6-methylguanine-DNA methyltransferase) protein is an enzyme involved in DNA repair. It plays a critical role in removing alkyl groups from the O-6 position of guanine, which can be induced by alkylating agents or environmental factors. By removing these alkyl groups, MGMT helps maintain genomic stability and prevents mutations from occurring.
What is the function of MGMT protein?
The function of MGMT protein is essential for protecting cells against the detrimental effects of alkylating agents, such as chemotherapy drugs or environmental toxins. Its role in DNA repair makes it an important target for cancer treatment, as the presence of functional MGMT protein in tumor cells can confer resistance to alkylating chemotherapy drugs.
MGMT related signaling pathway
The signaling pathway related to MGMT involves its activation and subsequent participation in the DNA repair process. Upon exposure to alkylating agents, MGMT is transcriptionally induced and its protein levels are increased. MGMT acts as a suicide enzyme, as it irreversibly transfers the alkyl group from the damaged DNA molecule to its active site cysteine residue. This results in the inactivation of MGMT and the creation of a covalent bond between the protein and the alkyl group.
MGMT Related Diseases
- Glioblastoma multiforme: MGMT methylation status is a predictive biomarker for response to alkylating agents, such as temozolomide, in patients with glioblastoma. MGMT promoter methylation can lead to reduced expression of MGMT protein in tumor cells, making them more sensitive to chemotherapy.
- Alkylating agent toxicity: Deficiency or decreased activity of MGMT protein can increase susceptibility to DNA damage caused by exposure to alkylating agents, leading to increased risk of tumors and other diseases.
- Cancer therapy: MGMT is associated with resistance to alkylating chemotherapy drugs such as temozolomide. Low levels of MGMT expression in cancer cells make them more susceptible to the damage caused by these drugs. Therefore, assessing MGMT levels can help predict the response to chemotherapy and guide treatment decisions.
Biomedical Application of MGMT Protein
- Cancer therapy: MGMT is associated with resistance to alkylating chemotherapy drugs such as temozolomide. Low levels of MGMT expression in cancer cells make them more susceptible to the damage caused by these drugs. Therefore, assessing MGMT levels can help predict the response to chemotherapy and guide treatment decisions.
- Tumor biomarker: MGMT promoter methylation status is frequently analyzed as a biomarker in cancer research. Hypermethylation of the MGMT promoter region is associated with reduced MGMT expression and increased sensitivity to alkylating agents. It is used as a predictive marker for response to therapy in various cancers, including glioblastoma, colorectal cancer, and lung cancer.
Case Study
(Cunpeng Nie, 2020)
Fig3. (A) Relative MGMT mRNA levels in T98G cells with different treatments: (1) PBS, (2) free DNAzyme, (3) 40 and (4) 80 μg/mL of Mn-MSN/DNAzyme. (B) Western blot analysis of MGMT protein expression. (C) Immunofluorescence analysis of MGMT protein expression in cells with different treatments.
(Kaouthar Bouzinab, 2020)
Fig4. Cellular characterization of protein expression. (a) Western blot analysis of membrane bound receptors responsible for AFt uptake and intracellular proteins responsible for TMZ resistance.
Quality Guarantee
High Purity
Fig1. SDS-PAGE (MGMT-5304H)
High Bioactivity & Detection Sensitivity
Fig2. Alkylating agents are potent carcinogens that can result in cell death, mutation and cancer. The protein encoded by this gene is a DNA repair protein that is involved in cellular defense against mutagenesis and toxicity from alkylating agents. The protein catalyzes transfer of methyl groups from O(6)-alkylguanine and other methylated moieties of the DNA to its own molecule, which repairs the toxic lesions. Methylation of the genes promoter has been associated with several cancer types, including colorectal cancer, lung cancer, lymphoma and glioblastoma.
Involved Pathway
MGMT involved in several pathways and played different roles in them. We selected most pathways MGMT participated on our site, such as DNA Damage Reversal,DNA Repair,MGMT-mediated DNA damage reversal, which may be useful for your reference. Also, other proteins which involved in the same pathway with MGMT were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
| Pathway Name | Pathway Related Protein |
|---|---|
| DNA Repair | KIAA1530,BABAM1,ZBTB32,DDB1,PPP4CB,BRCC3,POLI,MAD2L2,RTEL1,CETN2 |
| DNA Damage Reversal | ASCC2,ALKBH3,ALKBH2,ASCC1,ASCC3 |
Protein Function
MGMT has several biochemical functions, for example, DNA binding,DNA-methyltransferase activity,calcium ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by MGMT itself. We selected most functions MGMT had, and list some proteins which have the same functions with MGMT. You can find most of the proteins on our site.
| Function | Related Protein |
|---|---|
| damaged DNA binding | APEX1,CRY-DASH,POLK,MPG,RAD18,TP53BP1,CREBBP,CRY2,UNG,RAD1 |
| DNA binding | FLI1B,SPO11,ZNF711,MLXIPL,ZNF167,WBP7,MEIS2B,GLIS2,GTF2F2A,DNTTIP1 |
| methyltransferase activity | PRDM11,PRMT5,PRMT10,WBSCR22,DNMT3AB,PRMT9,RNMTL1A,TOMT,SMYD2A,NSUN5 |
| DNA-methyltransferase activity | DNMT3AB,DNMT3A,RNMTL1A,PRMT8B,DNMT3B,FBLL1,RNMTL1B,PRDM11,NDUFAF5,TRMT10B |
| calcium ion binding | MMP10,NINL,PCDH1G29,LPCAT1,CELSR3,DST,EHD2B,SLC25A25,NUCB2,KCNIP1B |
Interacting Protein
MGMT has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with MGMT here. Most of them are supplied by our site. Hope this information will be useful for your research of MGMT.
q81u00_bacan;ssdna_dcdgm
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References
- Stark, AM; Doukas, A; et al. Expression of DNA mismatch repair proteins MLH1, MSH2, and MSH6 in recurrent glioblastoma. NEUROLOGICAL RESEARCH 37:95-105(2015).
- Olah, Z; Kalman, J; et al. Proteomic Analysis of Cerebrospinal Fluid in Alzheimer's Disease: Wanted Dead or Alive. JOURNAL OF ALZHEIMERS DISEASE 44:1303-1312(2015).
