https://transhumanist.ru/index.php?action=history&feed=atom&title=TOP1 2026-04-11T13:00:25Z История изменений этой страницы в вики MediaWiki 1.43.6 https://transhumanist.ru/index.php?title=TOP1&diff=4320&oldid=prev 2021-04-29T19:11:55Z

<p>Новая страница: «DNA topoisomerase 1 (EC 5.6.2.1) (DNA topoisomerase I) ==Publications== {{medline-entry |title=<a href="/index.php?title=UCHL3&amp;action=edit&amp;redlink=1" class="new" title="UCHL3 (страница не существует)">UCHL3</a> Regulates Topoisomerase-Induced Chromosomal Break Repai...»</p> <p><b>Новая страница</b></p><div>DNA topoisomerase 1 (EC 5.6.2.1) (DNA topoisomerase I)<br /> <br /> ==Publications==<br /> <br /> {{medline-entry<br /> |title=[[UCHL3]] Regulates Topoisomerase-Induced Chromosomal Break Repair by Controlling [[TDP1]] Proteostasis.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29898404<br /> |abstract=Genomic damage can feature DNA-protein crosslinks whereby their acute accumulation is utilized to treat cancer and progressive accumulation causes neurodegeneration. This is typified by tyrosyl DNA phosphodiesterase 1 ([[TDP1]]), which repairs topoisomerase-mediated chromosomal breaks. Although [[TDP1]] levels vary in multiple clinical settings, the mechanism underpinning this variation is unknown. We reveal that [[TDP1]] is controlled by ubiquitylation and identify [[UCHL3]] as the deubiquitylase that controls [[TDP1]] proteostasis. Depletion of [[UCHL3]] increases [[TDP1]] ubiquitylation and turnover rate and sensitizes cells to [[TOP1]] poisons. Overexpression of [[UCHL3]], but not a catalytically inactive mutant, suppresses [[TDP1]] ubiquitylation and turnover rate. [[TDP1]] overexpression in the topoisomerase therapy-resistant rhabdomyosarcoma is driven by [[UCHL3]] overexpression. In contrast, [[UCHL3]] is downregulated in spinocerebellar ataxia with axonal neuropathy (SCAN1), causing elevated levels of [[TDP1]] ubiquitylation and faster turnover rate. These data establish [[UCHL3]] as a regulator of [[TDP1]] proteostasis and, consequently, a fine-tuner of protein-linked DNA break repair.<br /> |mesh-terms=* Cell Line, Tumor<br /> * Chromosome Breakage<br /> * Cysteine Endopeptidases<br /> * DNA Repair<br /> * DNA Topoisomerases, Type I<br /> * Down-Regulation<br /> * HEK293 Cells<br /> * Humans<br /> * Nucleotidases<br /> * Phosphoric Diester Hydrolases<br /> * Proteostasis<br /> * RNA Interference<br /> * RNA, Small Interfering<br /> * Ubiquitin<br /> * Ubiquitin Thiolesterase<br /> * Ubiquitination<br /> * Up-Regulation<br /> |keywords=* SCAN1<br /> * TDP<br /> * UCHL3<br /> * aging<br /> * cancer<br /> * heart failure<br /> * myocardial infarction<br /> * neurodegeneration<br /> * rhabdosarcoma<br /> * topoisomerase<br /> |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019701<br /> }}<br /> {{medline-entry<br /> |title=mir-24 activity propagates stress-induced senescence by down regulating DNA topoisomerase 1.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26748253<br /> |abstract=MicroRNAs (miRNAs) are a group of small non-coding executor RNAs. Their function as key modulators of cellular senescence has been widely recognized recently. By cross-comparing several human aging models we previously identified dozens of miRNAs being differentially regulated during aging. Here the functions of two miRNAs, mir-24 and mir-424, were investigated in an oxidative stress-induced fibroblast premature senescence model. Using pre-miRNA precursors, miRNAs were overexpressed in cells undergoing premature senescence induced by oxidative stress. More senescent cells were observed in mir-24 transfected cells. p53 was upregulated in mir-24 overexpressing cells, but downregulated in mir-424 overexpressing cells. DNA topoisomerase I ([[TOP1]]), an enzyme controlling DNA topology, was identified as a target of mir-24, whose expression was induced by oxidative stress. Knocking down [[TOP1]] induced cellular senescence. These results suggest that mir-24 activity propagates stress-induced senescence by down regulating [[TOP1]]. <br /> |mesh-terms=* Cells, Cultured<br /> * Cellular Senescence<br /> * DNA Topoisomerases, Type I<br /> * Down-Regulation<br /> * Fibroblasts<br /> * Gene Expression Regulation<br /> * Humans<br /> * MicroRNAs<br /> * Oxidative Stress<br /> * Transfection<br /> |keywords=* Cellular senescence<br /> * Oxidative stress<br /> * TOP1<br /> * miRNA<br /> * mir-24<br /> |full-text-url=https://sci-hub.do/10.1016/j.exger.2015.12.012<br /> }}</div>

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