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dual specificity phosphatase 1 OKDB#: 5124
 Symbols: DUSP1 Species: human
 Synonyms: HVH1, MKP1, CL100, MKP-1, PTPN10  Locus: 5q35.1 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment NCBI Summary: The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy. [provided by RefSeq, Aug 2017]
General function Enzyme
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function Follicle atresia
Comment DUSP1 regulates cell cycle progression and apoptosis in cumulus cells by affecting mitochondrial function, oxidative stress, and autophagy. Fu XH et al. (2019) Dual-specificity phosphatase 1 (DUSP1) is differentially expressed in cumulus cells of different physiological states, but its specific function and mechanism of action remain unclear. In this study, we explored the effects of DUSP1 expression inhibition on cell cycle progression, proliferation, apoptosis, and lactate and cholesterol levels in cumulus cells and examined reactive oxygen species levels, mitochondrial function, autophagy, and the expression of key cytokine genes. The results showed that inhibition of DUSP1 in cumulus cells caused abnormal cell cycle progression, increased cell proliferation, decreased apoptosis rates, increased cholesterol synthesis and lactic acid content, and increased cell expansion. The main reason for these effects was that inhibition of DUSP1 reduced ROS accumulation, increased GSH level and mitochondrial membrane potential, and reduced autophagy levels in cells. These results indicate that DUSP1 limits the biological function of bovine cumulus cells under normal physiological conditions and will greatly contribute to further explorations of the physiological functions of cumulus cells and the interactions of the cumulus-oocyte complex.//////////////////
Expression regulated by Growth Factors/ cytokines, FGF2
Comment Regulation of Dual Specificity Phosphatases by Fibroblast Growth Factor signaling pathways in bovine granulosa cells. Relav L et al. (2021) Controling the duration and amplitude of mitogen activated protein kinase (MAPK) signaling is an important element in deciding cell fate. One group of intracellular negative regulators of MAPK activity is a subfamily of the dual specificity phosphatase (DUSP) superfamily, of which up to 16 members have been described in ovarian granulosa cells. Growth factors stimulate proliferation of granulosa cells through MAPK, PKC and AKT pathways, although it is not known which pathways control DUSP expression in these cells. The aim of the present study was to identify which pathways are involved in the regulation of DUSP expression using a well-established serum-free culture system for bovine granulosa cells. Stimulation of cells with FGF2 increased DUSP1, DUSP5 and DUSP6 mRNA abundance in a time and dose-dependent manner, and increased DUSP5 and DUSP6 protein accumulation. None of the other eleven DUSP measured were regulated by FGF2. Pharmacological inhibition of MAPK3/1 signaling decreased FGF2-stimulated DUSP1, DUSP5 and DUSP6 mRNA levels (p < 0.05) whereas inhibition of PKC did not affect the expression of these three DUSPs. Abundance of FGF2-dependent DUSP6 mRNA was reduced by inhibition of PLC or by chelating calcium, but DUSP5 mRNA abundance was not affected. Abundance of basal DUSP1 and DUSP6, but not DUSP5, mRNA was increased by the addition of the calcium ionophore A23187. We conclude that FGF2 stimulation of DUSP5 abundance requires MAPK3/1 whereas DUSP6 mRNA accumulation is dependent on calcium signaling as well as MAPK3/1 activation, suggesting complex regulation of physiologically important DUSPs in the follicle.//////////////////
Ovarian localization Oocyte, Cumulus
Comment highly expressed in the ovary based ON PROTEIN ATLAS.
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: Feb. 2, 2015, 4:52 a.m. by: system   email:
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last update: Sept. 8, 2021, 9:48 p.m. by: hsueh    email:



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