DUSP6

DUSP6

A gene on chromosome 12q22-q23 that encodes dual-specificity phosphatase 6, a protein which downregulates MAP kinases of the ERK family.
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However, in AD patients, tau protein is abnormally hyperphosphorylated and contains five to nine phosphate groups, and is dissociated from microtubules and aggregates in neuron soma and dendrites to form NFTs.[72] In M17D cells, miR-34a directly combines with the 3'-UTR of MAP-tau to inhibit the expression of endogenous tau protein.[73] In addition, miR-125b activates kinases, such as ERK1/2 and CDK5/P35, by inhibiting the expression of DUSP6 and PPP1CA , thus leading to hyperphosphorylation of tau protein.[74] Related clinical studies have found that the blood of mild cognitive impairment (MCI) and dementia of Alzheimer-type (DAT) patients contains lower levels of exosomal miR-193b compared with that in controls, with lower content in DAT patients compared to that in patients with MCI.
This resulted in significant gene specific knockdown effects in the adult heart exhibited by downregulation of the Aldh1a2 and Dusp6 proteins [220].
FGFR1, FGF8 and Related Genes (FGF17, IL17RD, DUSP6, SPRY4, FLRT3, and KLB) (20,27,28)
DUSP1, DUSP5, and DUSP6 are suggested as hypoxia-sensitive and responsible for ERK downregulation [17, 18].
Term Count P value Genes MAPK signaling pathway 13 0.0062 RPS6KA5, AKT1, MAP4K4, MAP3K5, PLA2G4A, DUSP2, FGF9, TGFBR1, MAP2K4, MKNK2, PPP3R1, FGF12, DUSP6 Endocytosis 10 0.010 IGF1R, ADRB3, FLT1, TGFBR1, PSD3, VPS4B, DNAJC6, PSD2, ARAP2, LDLRAP1 Axon guidance 7 0.042 EPHA5, SEMA6A, PLXNA1, PPP3R1, SEMA4C, L1CAM, SRGAP1 Insulin signaling 6 0.0076 AKT1, L1CAM, IGF1R, IRS2, pathway SOCS7, RHOQ Focal adhesion 4 0.021 VCAM1, L1CAM, ITGA4, CERCAM Table 2: Small molecules which might reverse the dysregulation of AD in EC and HIP regions.
DUSP6 is a novel transcriptional target of p53 and regulates p53-mediated apoptosis by modulating expression levels of Bcl2 family proteins.
In the study, the Stanford team fingered a protein called DUSP6 that interferes with the capacity of an important class of immune cells to respond to the presence of a foreign substance, such as those appearing on the surface of an invading pathogen or in a vaccine designed to stifle that invasion.
To date, at least 17 genes have been associated with KS and these include KAL1, FGFR1, PROK2, PROKR2, FGF8, HS6ST1, CHD7, WDR11, SEMA3A, FGF17, IL17RD, DUSP6, SPRY4, FLRT3, NELF, FEZF1, and CCDC141 (3).
DUSP5, DUSP6, DUSP8, and DUSP10 were found inside the group of middle expressed PTPs.
miRNA Expression level Cellular process miR-181a Upregulated by morphine Promote astrocyte-preferential differentiation of NSPCs miR-23b Upregulated by morphine Adult neurogenesis miR-190 Downregulated by fentanyl Adult neurogenesis miR-143 Upregulation by IGF-1 Promotes proliferation, neural differentiation, and cell survival miR-181c Upregulation by IGF1/LIF Enhanced self-renewal of NSPCs miRNA Molecular target Reference miR-181a Prox1/Notch2 [159] miR-23b Morphine receptor expression (MOR1) [160] miR-190 NeuroD [161] miR-143 PDGFRA, PRKCE, MAPK7, DSSP, DMP-1, [162] KRAS, and BCL-2 miR-181c PTPN11, PTPN22, PTEN, Dusp6, PBX3, ZEB2, [162] and IRF8
(44) Several genes important in the pathogenesis of pancreatic cancer such as APC, (45) TSLC/IGSF4, (46) SOCS-1, (47) cyclin D2, (48) RASSF1A, (49) WWOX, (50) RUNX3, (51) CDH13, (52) DUSP6, (53) HHIP, (54) and SLC5A8 (55) undergo aberrant methylation, leading to reduced expression or loss of expression.
During early reprogramming, Erk1 and Erk2 are activated as a consequence of the downregulation of the Dusp6 protein phosphatase.