Disease relevance of DUSP4

• Overexpression of mitogen-activated protein kinase phosphatases MKP1, MKP2 in human breast cancer [1].
• Antibody activity to herpesvirus hominis type 2 (HVH-2) in 151 women cured of cervical carcinoma (60 in situ, 91 invasive) and in 106 controls differed significantly, especially between the in situ (73%) and control (17%) groups [2].
• Our data further supported the association between HVH-2 and cervical anaplasia and indicated that CMV may also be implicated in its etiology [2].
• Taxonomic analysis of four selected strains based on 16S rRNA similarity examinations revealed two Gordonia sp. strains, VH2 and Kb2, and one Mycobacterium fortuitum strain, NF4, belonging to the first group as well as one Micromonospora aurantiaca strain, W2b, belonging to the second group [3].
• Linkage without a population association suggests that a gene encoded on 14q confers susceptibility to multiple sclerosis, although this is not any of the existing VH-2 polymorphisms [4].

High impact information on DUSP4

• Analysis of the distribution of selected polymorphic loci revealed evidence of linkage disequilibrium, particularly between VH2 and VH3 subclass loci, indicating that the subclasses are interdispersed in the human germ-line chromosome [5].
• Similar heat-induced aggregation, followed by partial resolubilization, was found with a distinct dual-specificity phosphatase MKP-1 but not with MKP-2 [6].
• Mitogen-activated protein kinase phosphatase 2: a novel transcription target of p53 in apoptosis [7].
• Interestingly, the p53-dependent induction of MKP2 is prominent only in the cellular response to stimuli leading to apoptosis but not to cell cycle arrest [7].
• Induction of MKP2 is highly responsive to oxidative stress in a p53-dependent manner [7].

Biological context of DUSP4

• Transfection of HVH2 into NIH3T3 cells inhibited the v-src and MEK-induced transcriptional activation of serum-responsive element containing promoter, consistent with the notion that HVH2 promotes the inactivation of MAP kinase [8].
• MKP-2 is a member of the mitogen-activated protein (MAP) kinase phosphatase family which has been suggested to play an important role in the feedback control of MAP kinase-mediated gene expression [9].
• In addition, the N-terminal region of HVH2 also displays sequence identity to the cell cycle regulator, Cdc25 phosphatase [8].
• The deduced amino acid sequence of HVH2 shows significant identity to the VH1-related dual specific phosphatase family [8].
• Conditional expression of MAP kinase phosphatase-2 protects against genotoxic stress-induced apoptosis by binding and selective dephosphorylation of nuclear activated c-jun N-terminal kinase [10].

Anatomical context of DUSP4

• Immunofluorescence studies with an epitope-tagged HVH2 showed that the enzyme was localized in cell nucleus [8].
• Here we characterize a new MAP kinase phosphatase, MKP-2, that is induced in human peripheral blood T cells with phorbol 12-myristate 13-acetate and is expressed in a variety of nonhematopoietic tissues as well [11].
• Treatment of these cancer cell lines with the proteasome inhibitor ZLLF-CHO increased MKP-1 but not MKP-2 expression and decreased ERK1/2 phosphorylation [12].
• In PC12 cells, MKP1 and MKP2 are transcriptionally induced following stimulation by nerve growth factor [13].
• TYP 1 is not expressed in human fibroblasts unlike other CL100-like genes [14].

Associations of DUSP4 with chemical compounds

• Through site-directed mutagenesis, we defined the ERK/p38-binding site as a cluster of arginine residues in the NH(2)-terminal domain of MKP-2 [9].
• We demonstrate that Flag-WT-MKP-2 is able to rescue cells from apoptotic commitment when subjected to UV-C or cisplatin treatment [10].
• The levels of a dual specificity tyrosine phosphatase, MKP2, were significantly decreased in cerebellar vermis (1716 +/- 465 versus 2372 +/- 429 arbitrary units, U = 12, p < .02) from schizophrenic patients [15].
• We found that both inhibited the increase in expression of many of the genes, including IL-2 and MKP-2, that were induced early after stimulation of lymphocytes with phorbol myristate acetate and ionomycin [16].
• Thereby, strains VH2, Kb2, and NF4 directly adhered to and merged into the rubber material, while strain W2b produced mycelial corridors, especially on the surface of IR [3].

Regulatory relationships of DUSP4

• However, MKP-2 is surprisingly only able to deactivate JNK in vivo [10].

Other interactions of DUSP4

• Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phosphatase catalytically [9].
• Taken together, these results suggest that pancreatic tumor cells expressing oncogenic K-ras compensate, in part, by upregulating the expression of MKP-2 to repress the ERK signaling pathway [17].
• Inhibition of Gluconeogenesis through Transcriptional Activation of EGR1 and DUSP4 by AMP-activated Kinase [18].
• CONCLUSION: We propose that the putative tumor suppressor genes Dusp 4 and Serpina 5 provide a major clue to the indolent behavior of SBTs [19].
• These results show that the role of MKP-2 in terminating JNK activity is determined by the translocation of JNK to the nucleus, which is under agonist-specific regulation and not a universal cellular response to stimulation [20].

Analytical, diagnostic and therapeutic context of DUSP4

• METHODS AND RESULTS: We measured MAPKs activities and the protein levels of MAPKs and MKPs (MKP-1 and MKP-2) in the myocardium explanted at the time of transplantation from patients with end-stage failure caused by idiopathic dilated cardiomyopathy (n = 5-7) [21].
• An enzyme immunoassay (EIA) was used for the detection of antibodies to Herpesvirus hominis type 1 and 2 (HVH-1 and HVH-2), SA8 and Herpesvirus simiae (HVB) in human and nonhuman primate sera [22].

References