UBB+1

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UBB+1 is shorthand for Ubiquitin-B+1, a frameshifted mutant arising from the Ubiquitin B gene.[1] UBB+1 is thought to arise from molecular misreading, a poorly understood process. Molecular misreading introduces dinucleotide deletions (e.g. ΔGA, ΔGU) into mRNA transcripts. These deletions are not present in genomic DNA. UBB+1 has been observed in the hallmarks of Alzheimer's Disease, as well as other tauopathies and in polyglutamine diseases (e.g.Huntington's disease) but not in synucleinopathies (e.g.Parkinson's disease). Since its discovery it has been shown in vitro and in vivo that UBB+1 inhibits the proteasome and gives rise to downstream effects (e.g. a behavioral phenotype; impaired contextual memory). In non-neuronal cells UBB+1 also accumulates suggesting a functional role in non-neuronal diseases. UBB+1 can be truncated by yeast ubiquitin hydrolase 1 (YUH1) and ubiquitin C-terminal hydrolase L3 UCHL3 despite of the fact that the glycine at position 76 as been substituted for a tyrosine.[2][3]

References[edit]

  1. ^ van Leeuwen FW, de Kleijn DP, van den Hurk HH, Neubauer A, Sonnemans MA, Sluijs JA, Köycü S, Ramdjielal RD, Salehi A, Martens GJ, Grosveld FG, Peter J, Burbach H, Hol EM (January 1998). "Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients". Science 279 (5348): 242–7. doi:10.1126/science.279.5348.242. PMID 9422699. 
  2. ^ Dennissen, F; Kholod N; Hermes DJ; Kemmerling N; Steinbusch HW; Dantuma NP; van Leeuwen FW (July 6, 2011). "Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3).". FEBSletters 585 (16): 2568–74. doi:10.1016/j.febslet.2011.06.037. PMID 21762696. 
  3. ^ Dennissen FJ, Kholod N, Steinbusch HW, Van Leeuwen FW (2010). "Misframed proteins and neurodegeneration: a novel view on Alzheimer's and Parkinson's diseases". Neurodegener Dis 7 (1-3): 76–9. doi:10.1159/000285510. PMID 20173331.