ArticleCell cycle (Georgetown, Tex.)2014
C/EBPα regulates CRL4(Cdt2)-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint.
Article in Cell cycle (Georgetown, Tex.), 2014. 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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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- CRL4AOncogene · 2021Article
- C/EBPβ suppresses keratinocyte autonomous type 1 IFN response and p53 to increase cell survival and susceptibility to UVB-induced skin cancer.Carcinogenesis · 2019Article
- CDT2-controlled cell cycle reentry regulates the pathogenesis of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2019Article
- Induction and Validation of Cellular Senescence in Primary Human Cells.Journal of visualized experiments : JoVE · 2018Article
- Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2018Article
- Activation of TNF-α/NF-κB axis enhances CRL4BMolecular oncology · 2018Article
- MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BMolecular therapy. Nucleic acids · 2018Article
- Review
- Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes.Oxidative medicine and cellular longevity · 2017Article
- KSP inhibitor SB743921 inhibits growth and induces apoptosis of breast cancer cells by regulating p53, Bcl-2, and DTL.Anti-cancer drugs · 2016Article
- Small molecule therapeutics targeting F-box proteins in cancer.Seminars in cancer biology · 2016Review
- The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications.Oncotarget · 2015Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The bZIP transcription factor, C/EBPα is highly inducible by UVB and other DNA damaging agents in keratinocytes. C/EBPα-deficient keratinocytes fail to undergo cell cycle arrest in G1 in response to UVB-induced DNA damage and mice lacking epidermal C/EBPα are highly susceptible to UVB-induced skin cancer. The mechanism through which C/EBPα regulates the cell cycle checkpoint in response to DNA damage is unknown. Here we report untreated C/EBPα-deficient keratinocytes have normal levels of the cyclin-dependent kinase inhibitor, p21, however, UVB-treated C/EBPα-deficient keratinocytes fail to up-regulate nuclear p21 protein levels despite normal up-regulation of Cdkn1a mRNA levels. UVB-treated C/EBPα-deficient keratinocytes displayed a 4-fold decrease in nuclear p21 protein half-life due to the increased proteasomal degradation of p21 via the E3 ubiquitin ligase CRL4(Cdt2). Cdt2 is the substrate recognition subunit of CRL4(Cdt2) and Cdt2 mRNA and protein levels were up-regulated in UVB-treated C/EBPα-deficient keratinocytes. Knockdown of Cdt2 restored p21 protein levels in UVB-treated C/EBPα-deficient keratinocytes. Lastly, the failure to accumulate p21 in response to UVB in C/EBPα-deficient keratinocytes resulted in decreased p21 interactions with critical cell cycle regulatory proteins, increased CDK2 activity, and inappropriate entry into S-phase. These findings reveal C/EBPα regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4(Cdt2) mediated degradation of p21.
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Registered trials
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