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PR-Set7 is Degraded in a ConditionalCul4A Transgenic Mouse Model of Lung Cancer

摘要:

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.

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作者单位: Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital University of Medical Science, Beijing 100020, China [1] hToracic 0ncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA [2] Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA [3] Division of Diagnostic Pathology, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA [4]
期刊: 《中国肺癌杂志》2015年6期 345-350页 MEDLINEISTICPKUCSCD
栏目名称: 基础研究
DOI: 10.3779/j.issn.1009-3419.2015.06.15
发布时间: 2015-08-05
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