Ubb — Ubiquitin B is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Symbol | UBB |
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| Full Name | Ubiquitin B |
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| Chromosomal Location | 17p13.1 |
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| NCBI Gene ID | 7327 |
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| Ensembl ID | ENSG00000104140 |
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| UniProt ID | P0CG48 |
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| Protein | Ubiquitin B |
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| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, ALS |
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UBB (Ubiquitin B) encodes polyubiquitin, the precursor protein for ubiquitin molecules. Ubiquitin is essential for protein degradation via the ubiquitin-proteasome system (UPS) and autophagy. Defects in ubiquitin metabolism are central to neurodegenerative diseases, where accumulation of ubiquitin-positive inclusions is a hallmark finding.
UBB produces polyubiquitin chains that are processed into单体 ubiquitin:
- Protein degradation: Ubiquitin tags proteins for proteasomal or lysosomal degradation[1]
- Signal transduction: Ubiquitin serves as a signaling molecule
- DNA repair: Ubiquitin participates in DNA damage response
- Endocytosis: Ubiquitin marks membrane proteins for endocytosis
- Quality control: Ubiquitin targets misfolded and damaged proteins
- Ubiquitin-positive neurofibrillary tangles and plaques in AD brain[2]
- UBB+1 frameshift mutation causes accumulation of abnormal ubiquitin
- Impaired proteasome function in AD neurons
- Ubiquitination defects contribute to protein aggregate accumulation
- Lewy bodies are ubiquitin-positive
- PARK2 (Parkin) is an E3 ubiquitin ligase
- PINK1 regulates parkin-mediated mitophagy
- UBB alterations in PD brain
- Mutant huntingtin is ubiquitinated
- Impaired UPS function in HD
- Ubiquitin-positive inclusions in HD brain
- Ubiquitin-positive inclusions in motor neurons
- Mutations in ubiquitin-related genes (UBQLN2, VCP)
- TDP-43 proteinopathy involves ubiquitination
- Proteasome enhancers
- UPS modulators
- Autophagy inducers as compensation for UPS dysfunction
- Hershko A, Ciechanover A (1998). The ubiquitin system. Annu Rev Biochem. PMID:9734497
- Dawson TM, Dawson VL (2003). Ubiquitin metabolism in neurodegenerative disease. J Clin Invest. PMID:12840061
- Rothenberg C, et al. (2010). Ubiquitin accumulation in neurodegeneration. Nat Rev Neurosci. PMID:20720502
- Zheng Q, et al. (2018). UBB+1 and proteasome dysfunction in AD. Mol Neurodegener. PMID:30545386
Research platforms for UBB:
- Transgenic Mice: Ubiquitin overexpression
- Knockout Studies: Conditional deletions
- Cell Culture: Neuronal stress models
- iPSC Models: Patient-derived neurons
Targeting ubiquitin system:
- Proteasome Modulators: Enhancing or inhibiting degradation
- Deubiquitinase Inhibitors: DUB targeting
- UPS Enhancers: Improving protein clearance
- Gene Therapy: Modulating ubiquitin expression
The study of Ubb — Ubiquitin B has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Hershko A, Ciechanover A (1998). "The ubiquitin system." Annual Review of Biochemistry. PMID:9734497
- Dawson TM, Dawson VL (2003). "Ubiquitin metabolism in neurodegenerative disease." Journal of Clinical Investigation. PMID:12840061
- Rothenberg C, et al. (2010). "Ubiquitin accumulation in neurodegeneration." Nature Reviews Neuroscience. PMID:20720502
- Zheng Q, et al. (2018). "UBB+1 and proteasome dysfunction in AD." Molecular Neurodegeneration. PMID:30545386
- Layfield R, et al. (2005). " ubiquitination and neurodegenerative disease." Brain Research Reviews. PMID:15936065
- Tan JM, et al. (2008). "Ubiquitin- and ubiquitin-like proteins in neurodegeneration." Journal of Neurochemistry. PMID:18208540