@article{oai:kanazawa-u.repo.nii.ac.jp:00027465,
 author = {Shamma, Awad and Tagami, Yujiro and Miki, Takao and Kitajima, Shunsuke and Noda, Makoto and Obara, Takao and Okamoto, Takahiro and Takahashi, Chiaki},
 issue = {4},
 journal = {Cancer Cell},
 month = {Apr},
 note = {Oncogene-induced cellular senescence is well documented, but little is known about how infinite cell proliferation induced by loss of tumor suppressor genes is antagonized by cellular functions. Rb heterozygous mice generate Rb-deficient C cell adenomas that progress to adenocarcinomas following biallelic loss of N-ras. Here, we demonstrate that pRb inactivation induces aberrant expression of farnesyl diphosphate synthase, many prenyltransferases, and their upstream regulators sterol regulatory element-binding proteins (SREBPs) in an E2F-dependent manner, leading to enhanced isoprenylation and activation of N-Ras. Consequently, elevated N-Ras activity induces DNA damage response and p130-dependent cellular senescence in Rb-deficient cells. Furthermore, Rb heterozygous mice additionally lacking any of Ink4a, Arf, or Suv39h1 generated C cell adenocarcinomas, suggesting that cellular senescence antagonizes Rb-deficient carcinogenesis. © 2009 Elsevier Inc. All rights reserved.},
 pages = {255--269},
 title = {Rb Regulates DNA Damage Response and Cellular Senescence through E2F-Dependent Suppression of N-Ras Isoprenylation},
 volume = {15},
 year = {2009}
}