@article{oai:sapmed.repo.nii.ac.jp:00014168,
 author = {Mita, Hiroaki and Toyota, Minoru and Sasaki, Yasushi and Suzuki, Hiromu and Idogawa, Masashi and Kashima, Lisa and Tokino, Takashi},
 journal = {Tumor Research, Tumor Research},
 month = {},
 note = {Cell cycle progression is monitored by checkpoint mechanisms to ensure the integrity of the genome. CHFR which contains a RING domain and has ubiquitin ligase activity, a novel mitotic checkpoint gene, delays chromosome condensation in cells treated with microtubule poisons. CHFR is inactivated by promoter methylation and point mutations in various human tumors, and cancer cells lacking CHFR are sensitive to microtubule inhibitors. However, few reports are available on the molecular mechanism that accounts for the link between the sensitivity of cancer cells to microtubule inhibitors and the physiological function of CHFR. In the present study, we isolated cellular proteins capable of interacting with CHFR using yeast two-hybrid method to clarify the function of CHFR. As a result of the screening, we isolated canonical and noncanonical E2 ubiquitin conjugating enzymes as CHFR interacting proteins, which are involved in proteolytic and non-proteolytic ubiquitination respectively. This raises the possibility that CHFR is switching canonical and noncanonical ubiquitination depending on the situation of cells. On the other hand, we isolated gadd34 which interacted with the FHA domain of CHFR by two-hybrid screen. Coexpression in mammalian cells showed that gadd34 interacted with the FHA domain of CHFR, but gadd34 is not the substrate for CHFR, rather it promoted autoubiquitination of CHFR. Furthermore, CHFR moved, in part, from nucleus to cytoplasm in the presence of microtubule inhibitor docetaxel, which enabled colocalization of CHFR and gadd34 in cytoplasm. This colocalization was followed by cell death. These findings suggest that gadd34 and CHFR cooperate to mediate cell death in response to mitotic stress.},
 pages = {23--41},
 title = {Proteins interacting with CHFR, mitotic-checkpoint ubiquitin ligase},
 volume = {41},
 year = {2006}
}