UBB+1 explained

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's ubiquitin hydrolase 1 (YUH1)^[2] and ubiquitin C-terminal hydrolase L3 UCHL3 even though the glycine at position 76 has been substituted for a tyrosine.^{[3] [4]}

Notes and References

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 . Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients . Science . 279 . 5348 . 242–7 . January 1998 . 9422699 . 10.1126/science.279.5348.242.
2. Web site: 2023-04-08 . P35127 UBL1_YEAST . uniprot.org .
3. Dennissen. F. Kholod N . Hermes DJ . Kemmerling N . Steinbusch HW . Dantuma NP . van Leeuwen FW . Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3).. FEBS Letters. July 6, 2011. 10.1016/j.febslet.2011.06.037. 21762696. 585. 16. 2568–74. 28207136. free.
4. Dennissen FJ, Kholod N, Steinbusch HW, Van Leeuwen FW . Misframed proteins and neurodegeneration: a novel view on Alzheimer's and Parkinson's diseases . Neurodegener Dis . 7 . 1–3 . 76–9 . 2010 . 20173331 . 10.1159/000285510 . 207749046 .