Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human MnSOD gene has a typical housekeeping gene promoter, but is highly inducible by various physical, chemical, and biological agents. Transcription factors SP-1 and AP-2 seem to have opposite roles in the transcriptional activity of the basal promoter. Whereas SP-1 plays a positive role, which is absolutely essential for transcription from the human MnSOD promoter, AP-2 appears to play a negative role in this process. An enhancer element is found in the promoter region of the human MnSOD gene. Several important enhancer elements are located in the second intron. The NF-kappa B site in the second intron is essential but not sufficient for high-level induction of MnSOD by cytokines. Although mutations in the regulatory elements may be partially responsible for the lack of induction of MnSOD in some cell types, differences in the degree of induction exist that cannot be accounted for by the defect in the DNA sequence. It is highly likely that this difference is due to the presence or absence of coactivator or suppressor proteins in the cells and may have a physiological role in the defense against oxidative stress.
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PMID:Transcription regulation of human manganese superoxide dismutase gene. 1191 21

Mutations of the superoxide dismutase (SOD) genes are associated with neoplastic and non-neoplastic diseases. However, the existence of polymorphic mutations of manganese SOD (Mn-SOD) has not been explored in squamous cell carcinoma (SCC) cells or in normal cells. In the present study, we examined mutations in the 5' flanking region of the Mn-SOD gene and Mn-SOD mRNA using 10 human oral SCC (OSC) cell lines and intact lymphocytes obtained from 10 healthy donors and one patient with OSC. The polymerase chain reaction products of DNA obtained from lymphocytes revealed insertions at many sites (-1833, -1575, -1093, -1056, -325, -318, and -310) in 10 of the 11 donors. Transitions and (or) transversions were also observed at -1638 and -216 in lymphocytes from six donors and one donor, respectively. In DNA obtained from OSC cells, insertions and transitions and (or) transversions were more frequent than those in DNA from lymphocytes. In addition, deletions at -1341 and -1288 were observed in all lines except for one line. In these mutations, the transcription factor binding sites were not involved except for the AP-2 binding site (-102) in three cell lines. In Mn-SOD mRNA, Val at -9 position was varied to Ala in lymphocytes from two donors and three OSC cell lines, respectively. In the remaining cell lines, Mn-SOD mRNA from lymphocytes and OSC cell lines revealed heterozygosity (Ala/Val) and homozygosity (Val/Nal), respectively. The Mn-SOD activities in lymphocytes were 3.8-5.8 x 10(-4) U/10(6) cells and the activities in OSC cell lines were 1.8-8.3 x 10(-4) U/10(6) cells. These Mn-SOD activities were not correlated with the mutations of DNA and mRNA. From these results, it is indicated that polymorphic mutations of Mn-SOD exist in human normal cells and that the deletions might be obtained in the course of malignant transformation of OSC although decrease in Mn-SOD activity is not involved in the transformation.
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PMID:Polymorphic mutations of the Mn-SOD gene in intact human lymphocytes and oral squamous cell carcinoma cell lines. 1268 35

MnSOD, which is an important oxygen free radical scavenger in organisms, has an effect to resist oxidative stress and tumor. The expression and regulation of MnSOD gene is a complicated process, which includes many kinds of transcription factors, cell signal molecules and cell signal pathways. It refers to three aspects including transcription regulation, post-transcription regulation and translation regulation. Transcription regulation is the primary step for MnSOD gene expression and plays a key role during the expression of MnSOD gene. The activity of transcription factors, which controls MnSOD gene expression, such as SP-1, AP-2, AP-1, NF-kB and so on, can be changed in the course of transcription regulation. Drugs and metalions can also affect those transcription factors' activity. Furthermore some genes mutation and depletion also have an influence on the activity of those transcription factors. Post-transcription regulation is in a way of changing the stability of mRNA and its translation. Translation regulation is a process to regulate edition, modification, binding to metalion and site-specific of MnSOD polypeptide. Recently a kind of manganese trafficking factor for mitochondrial MnSOD called MTMl which is very important for activation of MnSOD has been discovered. Here, we review the advances in this field with an emphasis on transcription regulation and translation regulation of MnSOD gene. And at last, we discussed the prospect of MnSOD gene expression and regulation.
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PMID:[Advances in the expression and regulation of MnSOD gene]. 1877 24