title: PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer.
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.
authors.affiliation: Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital University of Medical Science, Beijing 100020, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hsieh
authors.affiliation: Division of Diagnostic Pathology, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Au
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.affiliation: Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital University of Medical Science, Beijing 100020, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: You
mesh_terms: D000818:Animals; D002453:Cell Cycle; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D059748:Proteolysis; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D044842:Cullin Proteins; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D014404:Tubulin; C114234:CUL4A protein, human; C529566:KMT5a protein, mouse