ArticleMolecular and cellular biochemistry2012
Lamin misexpression upregulates three distinct ubiquitin ligase systems that degrade ATR kinase in HeLa cells.
Article in Molecular and cellular biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 29 citations in OpenAlex.
- E3 ubiquitin ligase HECW2: a promising target for tumour therapy.Cancer cell international · 2024Review
- AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition.iScience · 2023Article
- Chromatin and Cancer: Implications of Disrupted Chromatin Organization in Tumorigenesis and Its Diversification.Cancers · 2023Review
- The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis.Stem cells and cloning : advances and applications · 2023Review
- The Biology of the Nuclear Envelope and Its Implications in Cancer Biology.International journal of molecular sciences · 2019Review
- Role of lamin b1 in chromatin instability.Molecular and cellular biology · 2015Article
- Novel functions and targets of miR-944 in human cervical cancer cells.International journal of cancer · 2015Article
- Sustained accumulation of prelamin A and depletion of lamin A/C both cause oxidative stress and mitochondrial dysfunction but induce different cell fates.Nucleus (Austin, Tex.) · 2015Article
- Identification of acquired mutations by whole-genome sequencing in GATA-2 deficiency evolving into myelodysplasia and acute leukemia.Annals of hematology · 2014Article
- The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the metaphase to anaphase transition.The Journal of biological chemistry · 2013Article
- Article
- Lamin A/C haploinsufficiency modulates the differentiation potential of mouse embryonic stem cells.PloS one · 2013Article
- Ubiquitin ligase RNF123 mediates degradation of heterochromatin protein 1α and β in lamin A/C knock-down cells.PloS one · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Lamins are the major structural components of the nucleus and mutations in the human lamin A gene cause a number of genetic diseases collectively termed laminopathies. At the cellular level, lamin A mutations cause aberrant nuclear morphology and defects in nuclear functions such as the response to DNA damage. We have investigated the mechanism of depletion of a key damage sensor, ATR (Ataxia-telangiectasia-mutated-and-Rad3-related) kinase, in HeLa cells expressing lamin A mutants or lamin A shRNA. The degradation of ATR kinase in these cells was through the proteasomal pathway as it was reversed by the proteasomal inhibitor MG132. Expression of lamin A mutants or shRNA led to transcriptional activation of three ubiquitin ligase components, namely, RNF123 (ring finger protein 123), HECW2 (HECT domain ligase W2) and the F-box protein FBXW10. Ectopic expression of RNF123, HECW2 or FBXW10 directly resulted in proteasomal degradation of ATR kinase and the ring domain of RNF123 was required for this degradation. However, these ligases did not alter the stability of DNA-dependent protein kinase, which is not depleted upon lamin misexpression. Although degradation of ATR kinase was reversed by MG132, it was not affected by the nuclear export inhibitor, leptomycin B, suggesting that ATR kinase is degraded within the nucleus. Our findings indicate that lamin misexpression can lead to deleterious effects on the stability of the key DNA damage sensor, ATR kinase by upregulation of specific components of the ubiquitination pathway.
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