PR-Set7 is Degraded in a ConditionalCul4A Transgenic Mouse Model of Lung Cancer
10.3779/j.issn.1009-3419.2015.06.15
- Author:
WANG YANG
1
;
XU ZHIDONG
;
MAO JIAN-HUA
;
DavidHSIEH
;
AU ALFRED
;
JABLONS M DAVID
;
LI HUI
;
YOU LIANG
Author Information
1. Thoracic Surgery Department
- Keywords:
Lung neoplasms;
Cul4A;
AdenoCre;
Mouse model;
PR-Set7;
γ-tubulin;
Pericentrin;
Cell cycle
- From:
Chinese Journal of Lung Cancer
2015;(6):345-350
- CountryChina
- Language:Chinese
-
Abstract:
Background and objectiveMaintenance 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 atfer DNA damage. hTis might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity atfer 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 ifrst time that Cul4A is oncogenicin vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identiifed higher protein level changes of γ-tubulin and pericentrin by IHC.Results hTe level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identiifed higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre.Conclusion 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.
