https://transhumanist.ru/index.php?action=history&feed=atom&title=FBXO46FBXO46 - История изменений2026-06-21T01:13:01ZИстория изменений этой страницы в викиMediaWiki 1.43.6https://transhumanist.ru/index.php?title=FBXO46&diff=4609&oldid=prevOdysseusBot: Новая страница: «F-box only protein 46 (F-box only protein 34-like) [FBX46] [FBXO34L] ==Publications== {{medline-entry |title=The SCF ubiquitin ligase complex mediates degradat...»2021-04-29T19:26:17Z<p>Новая страница: «F-box only protein 46 (F-box only protein 34-like) [FBX46] [FBXO34L] ==Publications== {{medline-entry |title=The SCF ubiquitin ligase complex mediates degradat...»</p>
<p><b>Новая страница</b></p><div>F-box only protein 46 (F-box only protein 34-like) [FBX46] [FBXO34L]<br />
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==Publications==<br />
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{{medline-entry<br />
|title=The SCF ubiquitin ligase complex mediates degradation of the tumor suppressor [[FBXO31]] and thereby prevents premature cellular senescence.<br />
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30171069<br />
|abstract=The tumor suppressor F-box protein 31 ([[FBXO31]]) is indispensable for maintaining genomic stability. Its levels drastically increase following DNA damage, leading to cyclin D1 and [[MDM2]] degradation and G and G /M arrest. Prolonged arrest in these phases leads to cellular senescence. Accordingly, [[FBXO31]] needs to be kept at low basal levels in unstressed conditions for normal cell cycle progression during growth and development. However, the molecular mechanism maintaining these basal [[FBXO31]] levels has remained unclear. Here, we identified the F-box family SCF-E3 ubiquitin ligase [[FBXO46]] (SCF ) as an important proteasomal regulator of [[FBXO31]] and found that [[FBXO46]] helps maintain basal [[FBXO31]] levels under unstressed conditions and thereby prevents premature senescence. Using molecular docking and mutational studies, we showed that [[FBXO46]] recognizes an R[i]XX[/i]R motif located at the [[FBXO31]] C terminus to direct its polyubiquitination and thereby proteasomal degradation. Furthermore, [[FBXO46]] depletion enhanced the basal levels of [[FBXO31]], resulting in senescence induction. In response to genotoxic stress, [[ATM]] (ataxia telangiectasia-mutated) Ser/Thr kinase-mediated phosphorylation of [[FBXO31]] at Ser-278 maintained [[FBXO31]] levels. In contrast, activated [[ATM]] phosphorylated [[FBXO46]] at Ser-21/Ser-67, leading to its degradation via [[FBXO31]]. Thus, [[ATM]]-catalyzed phosphorylation after DNA damage governs [[FBXO31]] levels and [[FBXO46]] degradation via a negative feedback loop. Collectively, our findings reveal that [[FBXO46]] is a crucial proteasomal regulator of [[FBXO31]] and thereby prevents senescence in normal growth conditions. They further indicate that [[FBXO46]]-mediated regulation of [[FBXO31]] is abrogated following genotoxic stress to promote increased [[FBXO31]] levels for maintenance of genomic stability.<br />
|mesh-terms=* Cellular Senescence<br />
* F-Box Proteins<br />
* Genomic Instability<br />
* Humans<br />
* Molecular Docking Simulation<br />
* Phosphorylation<br />
* Proteasome Endopeptidase Complex<br />
* SKP Cullin F-Box Protein Ligases<br />
* Tumor Suppressor Proteins<br />
* Ubiquitination<br />
|keywords=* ATM<br />
* DNA damage<br />
* E3 ubiquitin ligase<br />
* F-box protein<br />
* cell cycle<br />
* flow cytometry<br />
* post-transcriptional regulation<br />
* post-translational modification (PTM)<br />
* protein motif<br />
* protein turnover<br />
* senescence<br />
* ubiquitin ligase<br />
* ubiquitination<br />
* ubiquitylation (ubiquitination)<br />
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200945<br />
}}</div>OdysseusBot