PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer
Background and objective. 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. Conclusion. PR-Set7 is a direct target ofmore »
- Capital University of Medical Science, Beijing (China). Thoracic Surgery Dept.
- Univ. of California, San Francisco, CA (United States). Thoracic Oncology Lab.
- Lawrence Berkeley National Lab., CA (United States). Life Sciences Div.
- Univ. of California, San Francisco, CA (United States). Div. of Diagnostic Pathology
- Publication Date:
- Grant/Contract Number:
- Accepted Manuscript
- Journal Name:
- Chinese Journal of Lung Cancer
- Additional Journal Information:
- Journal Volume: 18; Journal Issue: 6; Journal ID: ISSN 1009-3419
- China Association for Science and Technology
- Research Org:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org:
- Country of Publication:
- United States
- 59 BASIC BIOLOGICAL SCIENCES lung neoplasms; Cul4A; AdenoCre; mouse model; PR-Set7; γ-tubulin; pericentrin; cell cycle
- OSTI Identifier:
- Alternate Identifier(s):
- OSTI ID: 1212155