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Molecular misreading: the occurrence of frameshift proteins in different diseases
- Source :
- Biochemical Society Transactions, 34, 738-742. Portland Press, Ltd.
- Publication Year :
- 2006
- Publisher :
- Portland Press Ltd., 2006.
-
Abstract
- Neuronal homoeostasis requires a constant balance between biosynthetic and catabolic processes. Eukaryotic cells primarily use two distinct mechanisms for degradation: the proteasome and autophagy of aggregates by the lysosomes. We focused on the UPS (ubiquitin–proteasome system). As a result of molecular misreading, misframed UBB (ubiquitin B) (UBB+1) is generated. UBB+1 accumulates in the neuritic plaques and neurofibrillary tangles in all patients with AD (Alzheimer's disease) and in the neuronal and glial hallmarks of other tauopathies and in polyglutamine diseases such as Huntington's disease. UBB+1 is not present in synucleinopathies such as Parkinson's disease. We showed that UBB+1 causes UPS dysfunction, aggregation and apoptotic cell death. UBB+1 is also present in non-neurological cells, hepatocytes of the diseased liver and in muscles during inclusion body myositis. Other frequently occurring (age-related) diseases such as Type 2 (non-insulin-dependent) diabetes mellitus are currently under investigation. These findings point to the importance of the UPS in diseases and open new avenues for target identification of the main players of the UPS. Treatment of these diseases with tools (e.g. viral RNA interference constructs) to intervene with specific targets is the next step.
- Subjects :
- Genetics
Synucleinopathies
Proteasome Endopeptidase Complex
Transcription, Genetic
Ubiquitin B
biology
Ubiquitin
Molecular Sequence Data
Autophagy
Genetic Diseases, Inborn
Proteins
medicine.disease
Biochemistry
Frameshift mutation
Cell biology
Proteasome
biology.protein
medicine
Humans
Amino Acid Sequence
Senile plaques
Inclusion body myositis
Frameshift Mutation
Subjects
Details
- ISSN :
- 14708752 and 03005127
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Biochemical Society Transactions
- Accession number :
- edsair.doi.dedup.....5907cb6b1ec221a56c7af93dd5643ca4
- Full Text :
- https://doi.org/10.1042/bst0340738