https://transhumanist.ru/index.php?action=history&feed=atom&title=DDI2 2026-04-08T02:56:04Z История изменений этой страницы в вики MediaWiki 1.43.6 https://transhumanist.ru/index.php?title=DDI2&diff=6358&oldid=prev 2021-05-12T15:26:24Z

<p>Новая страница: «DDI1 homolog 2 (EC 3.4.23.-) ==Publications== {{medline-entry |title=Androgen receptor polyglutamine expansion drives age-dependent quality control defects and...»</p> <p><b>Новая страница</b></p><div>DDI1 homolog 2 (EC 3.4.23.-)<br /> <br /> ==Publications==<br /> <br /> {{medline-entry<br /> |title=Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29809168<br /> |abstract=Skeletal muscle has emerged as a critical, disease-relevant target tissue in spinal and bulbar muscular atrophy, a degenerative disorder of the neuromuscular system caused by a CAG/polyglutamine (polyQ) expansion in the androgen receptor ([[AR]]) gene. Here, we used RNA-sequencing (RNA-Seq) to identify pathways that are disrupted in diseased muscle using [[AR]]113Q knockin mice. This analysis unexpectedly identified substantially diminished expression of numerous ubiquitin/proteasome pathway genes in [[AR]]113Q muscle, encoding approximately 30% of proteasome subunits and 20% of E2 ubiquitin conjugases. These changes were age, hormone, and glutamine length dependent and arose due to a toxic gain of function conferred by the mutation. Moreover, altered gene expression was associated with decreased levels of the proteasome transcription factor [[NRF1]] and its activator [[DDI2]] and resulted in diminished proteasome activity. Ubiquitinated [[ADRM1]] was detected in [[AR]]113Q muscle, indicating the occurrence of stalled proteasomes in mutant mice. Finally, diminished expression of Drosophila orthologues of [[NRF1]] or [[ADRM1]] promoted the accumulation of polyQ [[AR]] protein and increased toxicity. Collectively, these data indicate that [[AR]]113Q muscle develops progressive proteasome dysfunction that leads to the impairment of quality control and the accumulation of polyQ [[AR]] protein, key features that contribute to the age-dependent onset and progression of this disorder.<br /> |mesh-terms=* Aging<br /> * Animals<br /> * Cell Adhesion Molecules<br /> * Intracellular Signaling Peptides and Proteins<br /> * Male<br /> * Mice<br /> * Mice, Transgenic<br /> * Muscle, Skeletal<br /> * Muscular Atrophy, Spinal<br /> * Nuclear Respiratory Factor 1<br /> * Peptides<br /> * Proteasome Endopeptidase Complex<br /> * Receptors, Androgen<br /> * Trinucleotide Repeat Expansion<br /> |keywords=* Muscle Biology<br /> * Neuromuscular disease<br /> * Neuroscience<br /> * Protein misfolding<br /> * Ubiquitin-proteosome system<br /> |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063498<br /> }}</div>

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