@article {221, title = {PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer.}, journal = {Zhongguo Fei Ai Za Zhi}, volume = {18}, year = {2015}, month = {2015 Jun}, pages = {345-50}, abstract = {

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 γ-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 γ-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.

}, keywords = {Animals, Cell Cycle, Cullin Proteins, Disease Models, Animal, Down-Regulation, Histone-Lysine N-Methyltransferase, Histones, Humans, Lung, Lung Neoplasms, Mice, Mice, Transgenic, Proteolysis, Tubulin}, issn = {1999-6187}, doi = {10.3779/j.issn.1009-3419.2015.06.15}, author = {Wang, Yang and Xu, Zhidong and Jiang-Hua Mao and Hsieh, David and Au, Alfred and Jablons, David M and Li, Hui and You, Liang} }