Disease relevance of DUSP5

• Using cDNA-microarray technology, we found that the expression of DUSP5 mRNA was dramatically increased by exogenous p53 in U373MG, a p53-mutant glioblastoma cell line [1].
• IUGR affected hepatic DUSP5 mRNA levels and exon 2 DNA methylation into adulthood in the rat [2].
• Variable region diversity in human circulating antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b. Preferential usage of two types of VH3 heavy chains [3].
• With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire [4].
• Three different phage clones expressing anti-HS single chain variable fragment antibodies (HS4C3, HS4D10, and HS3G8) were isolated, with an amino acid sequence of the complementarity-determining region 3 of GRRLKD (VH3 gene, DP-38), SLRMNGCGAHQ (VH3 gene, DP-42), and YYHYKVN (VH1 gene, DP-8), respectively [5].

Psychiatry related information on DUSP5

• FR3 amino acids 78-88 displayed the best-score epitopes in Ids containing a VH3-family segment, the most represented in FL Ids [6].

High impact information on DUSP5

• Infection with human immunodeficiency virus-type 1 (HIV-1) depletes T cells expressing CD4 and B cells expressing immunoglobulin (Ig) VH3 gene products [7].
• In contrast to the WA mRFs H chains in which VH1 genes are used, the 35G6 IgM expresses a VH3 gene [8].
• Restricted use of fetal VH3 immunoglobulin genes by unselected B cells in the adult. Predominance of 56p1-like VH genes in common variable immunodeficiency [9].
• In this study, we have sequenced a set of rearranged VH3 genes generated by genomic polymerase chain reaction (PCR) from normal adults and those with common variable immunodeficiency (CVI) [9].
• 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 [10].

Chemical compound and disease context of DUSP5

• We conclude that intrauterine growth retardation induced by uteroplacental insufficiency 1) affects the hepatic epigenetic characteristics and mRNA of the DUSP-5 and 2) increases hepatic insulin receptor substrate-1 phosphorylation at serine 612 in adult rats [2].

Biological context of DUSP5

• This binding determines the substrate specificity of DUSP5 in vivo, as it inactivates ERK2 but not Jun N-terminal protein kinase or p38 MAP kinase [11].
• If, as the results suggest, DUSP5 is a direct target of p53, it represents a novel mechanism by which p53 might negatively regulate cell-cycle progression by downregulating mitogen- or stress-activated protein kinases [1].
• Chromatin-immunoprecipitation (ChIP) and reporter assays demonstrated that endogenous p53 protein would bind directly to the promoter region of the DUSP5 gene, implying p53-dependent transcriptional activity [1].
• In addition, chromatin immunoprecipitation assays experimentally verified nine predicted SRF binding sites in T98G cells, including a previously unknown SRF site upstream of DUSP5 [12].
• Crystal structure of the catalytic domain of human DUSP5, a dual specificity MAP kinase protein phosphatase [13].

Anatomical context of DUSP5

• Moreover, we have identified a DUSP5-dependent negative regulatory pathway for MAPK activity in T cells [14].
• To determine whether Abs commonly expressed by V-preB+L+ B cells show similar features, we analyzed Ig H chains from three highly expressed VH families, VH1, VH3, and VH4, and Ig-lambda [15].
• RT-PCR amplification reveals expression of the MAPK-selective phosphatases (MKP), MKP-1, -3, and dual-specificity phosphatase 5, in granulosa cells [16].
• Progressive decrease in VH3 gene family expression in plasma cells of HIV-infected patients [17].
• Among naturally activated lymphocytes the VH6 gene was markedly over-represented, while expression of the VH1 and VH3 gene families was decreased [18].

Associations of DUSP5 with chemical compounds

• Dual-specificity phosphatase 5 (DUSP5), a VH1-like enzyme that hydrolyses nuclear substrates phosphorylated on both tyrosine and serine/threonine residues, has a potential role in deactivation of mitogen- or stress-activated protein kinases [1].
• DUSP Meet Immunology: Dual Specificity MAPK Phosphatases in Control of the Inflammatory Response [19].
• To examine directly the available human VH3 repertoire, we have used PCR to amplify and clone candidate germ-line VH3b H chain V region genes from two unrelated subjects from whom anti-Hib polysaccharide mAb had been previously obtained [20].
• Id-16/6 can identify a subgroup of VH3-derived antibodies we have termed the 18/2 CDR family [21].
• Bone marrow plasma cells from RIC contained short gamma 1 heavy-chain transcripts in which a VDJ exon related to the VH2 subgroup was directly joined to the hinge exon; plasma cells from THR contained short gamma 1 transcripts with a VDJ exon related to the VH3 subgroup joined to the CH3 exon [22].

Enzymatic interactions of DUSP5

• The mammalian members of this subfamily including hVH-3 commonly localize to the nucleus and exhibit catalytic activity toward phosphorylated extracellular signal-regulated kinase [23].

Regulatory relationships of DUSP5

• Three tumors expressed VH3 genes and one expressed a VH1 gene, while the light chains included two V lambda and one V kappa III; one light chain was not isolated [24].

Other interactions of DUSP5

• Overexpression of DUSP5 suppressed the growth of several types of human cancer cells, in which Erk1/2 was significantly dephosphorylated [1].
• This distribution frequency was different from that observed in RA, where VH3 was the dominant family, followed by VH1 [25].
• We have isolated a novel VH-1-like PTPase, hVH-3, from the human placenta and compared various aspects of its expression with previously isolated members of this subfamily [23].
• IgM, IgD and IgG that expressed a VH3 gene family segment, were decreased in patients with low CD4 counts and to a greater extend in patients with AIDS symptoms (up to 85% for IgG) compared to adult healthy donors [26].

Analytical, diagnostic and therapeutic context of DUSP5

• Binding to SPA in ELISA occurred with 15 of 15 VH3 IgM, but none of 12 IgM from the VH1, VH4, VH5, or VH6 families [27].
• DUSP expression was analyzed for possible correlation with patient age, disease stage, tumor grade, histological grade, chemotherapy status, and survival [28].
• In this study, we have performed sequence analysis of 104-day human fetal liver-derived, randomly isolated constant region C+ mu transcripts and demonstrate a consistent preference during fetal life for a small subset of three highly conserved VH3 family gene segments [29].
• Surface plasmon resonance measurements demonstrated that domain D and native SpA had the strongest binding interactions with an IgM-kappa encoded by the germline configuration of the VH3 gene VH26c [30].
• A larger number of clonally related VH sequences could be obtained by using a VH3 gene-specific PCR so that genealogical trees depicting the process of diversification could be drawn [31].

References