{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The DMWD gene encodes a widely expressed protein containing WD‐repeats that is positioned in the myotonic dystrophy (DM1) gene cluster on chromosome 19. Studies in mice show that although DMWD mRNA levels remain relatively constant during postnatal brain development, the protein – observed as a distinct 70‐kDa doublet – progressively increases and is enriched in neurons and the neuropil of regions dense with synaptic contacts. This localization suggests a role for DMWD in neural differentiation and synaptic function, which may contribute to the brain‐related symptoms displayed by DM1 patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, comparative sequence analysis has revealed that DMWD bears similarity to WDR20—a regulator of the deubiquitinases USP12 and USP46. Consistent with this structural relationship, experimental work has demonstrated that DMWD can directly bind both USP12 and USP46, stimulate USP12’s enzymatic activity, and differentially influence the subcellular localization of these enzymes. This implies that DMWD may help form distinct deubiquitinase complexes involved in regulating protein ubiquitination and turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Altered expression studies in DM1 patients further indicate that DMWD, together with its neighboring genes DMPK and SIX5, is subject to dysregulation that might contribute to disease pathogenesis. Quantitative analyses have revealed allele‐specific changes in DMWD mRNA levels that could influence the complex manifestation of DM1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the available findings support a multifaceted role for DMWD in the central nervous system and in pathways of protein homeostasis. Its postnatal upregulation in synapse‐rich areas and its partnership with key deubiquitinases suggest that DMWD may contribute both to normal neuronal function and to the molecular disturbances underlying the multisystem pathology of myotonic dystrophy.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jolanda H A M Westerlaken, Catharina E E M Van der Zee, Wilma Peters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The DMWD protein from the myotonic dystrophy (DM1) gene region is developmentally regulated and is present most prominently in synapse-dense brain areas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-8993(03)02430-2"}], "href": "https://doi.org/10.1016/s0006-8993(03"}, {"type": "t", "text": "02430-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12691844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12691844"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "G Jansen, D Bächner, M Coerwinkel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural organization and developmental expression pattern of the mouse WD-repeat gene DMR-N9 immediately upstream of the myotonic dystrophy locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (1995)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/4.5.843"}], "href": "https://doi.org/10.1093/hmg/4.5.843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7633444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7633444"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anne Olazabal-Herrero, Martin Bilbao-Arribas, Onintza Carlevaris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The dystrophia myotonica WD repeat-containing protein DMWD and WDR20 differentially regulate USP12 deubiquitinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.15875"}], "href": "https://doi.org/10.1111/febs.15875"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33844468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33844468"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maria Eriksson "}, {"type": "b", "children": [{"type": "t", "text": "Real-time RT-PCR for CTG repeat-containing genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Mol Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1385/1-59259-804-8:077"}], "href": "https://doi.org/10.1385/1-59259-804-8:077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15201450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15201450"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "M Eriksson, T Ansved, L Edstrom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Independent regulation of the myotonic dystrophy 1 locus genes postnatally and during adult skeletal muscle regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M001592200"}], "href": "https://doi.org/10.1074/jbc.M001592200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10748037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10748037"}]}]}]}