Редактирование: TOP1 (раздел)

==Publications==

{{medline-entry
|title=[[UCHL3]] Regulates Topoisomerase-Induced Chromosomal Break Repair by Controlling [[TDP1]] Proteostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29898404
|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.
|mesh-terms=* Cell Line, Tumor
* Chromosome Breakage
* Cysteine Endopeptidases
* DNA Repair
* DNA Topoisomerases, Type I
* Down-Regulation
* HEK293 Cells
* Humans
* Nucleotidases
* Phosphoric Diester Hydrolases
* Proteostasis
* RNA Interference
* RNA, Small Interfering
* Ubiquitin
* Ubiquitin Thiolesterase
* Ubiquitination
* Up-Regulation
|keywords=* SCAN1
* TDP
* UCHL3
* aging
* cancer
* heart failure
* myocardial infarction
* neurodegeneration
* rhabdosarcoma
* topoisomerase
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019701
}}
{{medline-entry
|title=mir-24 activity propagates stress-induced senescence by down regulating DNA topoisomerase 1.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26748253
|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]]. 
|mesh-terms=* Cells, Cultured
* Cellular Senescence
* DNA Topoisomerases, Type I
* Down-Regulation
* Fibroblasts
* Gene Expression Regulation
* Humans
* MicroRNAs
* Oxidative Stress
* Transfection
|keywords=* Cellular senescence
* Oxidative stress
* TOP1
* miRNA
* mir-24
|full-text-url=https://sci-hub.do/10.1016/j.exger.2015.12.012
}}