| First Author | Wang Y | Year | 2015 |
| Journal | Zhongguo Fei Ai Za Zhi | Volume | 18 |
| Issue | 6 | Pages | 345-50 |
| PubMed ID | 26104890 | Mgi Jnum | J:305886 |
| Mgi Id | MGI:6709427 | Doi | 10.3779/j.issn.1009-3419.2015.06.15 |
| Citation | Wang Y, et al. (2015) PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer. Zhongguo Fei Ai Za Zhi 18(6):345-50 |
| abstractText | BACKGROUND: Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. METHODS: We developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of gamma-tubulin and pericentrin by IHC. RESULTS: The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and gamma-tubulin in Cul4A mouse lungs induced by AdenoCre. CONCLUSIONS: PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model. |
