Disease relevance of DUSP10

• Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: implications for prostate cancer prevention by vitamin D [1].
• The ability of 1,25D to up-regulate MKP5 was maintained in primary prostatic adenocarcinoma cells but was absent in metastases-derived prostate cancer cell lines [1].

High impact information on DUSP10

• These studies reveal MKP5 as a mediator of p38 inactivation and decreased IL-6 expression by 1,25D in primary prostatic cultures of normal and adenocarcinoma cells, implicating decreased prostatic inflammation as a potential mechanism for prostate cancer prevention by 1,25D [1].
• We also identified a putative positive vitamin D response element within the MKP5 promoter that associated with the vitamin D receptor following 1,25D treatment [1].
• Using normal human prostatic epithelial cells, we examined the role of mitogen-activated protein kinase phosphatase 5 (MKP5) in mediating cancer preventive activities of vitamin D. Up-regulation of MKP5 mRNA by 1,25-dihydroxyvitamin-D3 (1,25D) was dependent on the vitamin D receptor [1].
• Treatment of prostate cells with 1,25D inhibited p38 phosphorylation, and MKP5 small interfering RNA blocked this effect [1].
• Here we have cloned and characterized a novel dual specificity phosphatase, which we have designated MKP-5 [2].

Biological context of DUSP10

• The MKP5 gene, which maps to human chromosome 1q32, is expressed tissue-specifically as two transcripts of approximately 3.4 and 2.4 kb in human liver and skeletal muscle [3].
• ATM-dependent activation of the gene encoding MAP kinase phosphatase 5 by radiomimetic DNA damage [4].
• We have determined the crystal structure of the catalytic domain of human MKP5 (MKP5-C) to 1.6 A [5].

Anatomical context of DUSP10

• MKP-5 mRNA is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli [2].

Associations of DUSP10 with chemical compounds

• Calcitriol induces MKP5 expression in prostate cells leading to the selective dephosphorylation and inactivation of the stress-activated kinase p38 [6].
• We found that PCa cell lines DU 145, PC-3, LNCaP and LAPC-4 retained the ability to up-regulate MKP5 following curcumin, resveratrol and [6]-gingerol exposure, suggesting utility of these phytochemicals in PCa treatment [7].

Other interactions of DUSP10

• MKP-4 and MKP-5 were uniformly absent [8].

Analytical, diagnostic and therapeutic context of DUSP10

• Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5 [2].

References