title: Radiosensitizing effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells.
abstract: The function of PSMC5 (proteasome 26S subunit, ATPase 5) in tumors, particularly with respect to cancer radioresistance, is not known. Here, we identified PSMC5 as a novel radiosensitivity biomarker, demonstrating that radiosensitive H460 cells were converted to a radioresistance phenotype by PSMC5 depletion. Exposure of H460 cells to radiation induced a marked accumulation of cell death-promoting reactive oxygen species, but this effect was blocked in radiation-treated H460 PSMC5-knockdown cells through downregulation of the p53-p21 pathway. Interestingly, PSMC5 depletion in H460 cells enhanced both AKT activation and MDM2 transcription, thereby promoting the degradation of p53 and p21 proteins. Furthermore, specific inhibition of AKT with triciribine or knockdown of MDM2 with small interfering RNA largely restored p21 expression in PSMC5-knockdown H460 cells. Our data suggest that PSMC5 facilitates the damaging effects of radiation in radiation-responsive H460 cancer cells and therefore may serve as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients.
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea; Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Hong Shik
authors.initials: HS
authors.lastname: Yun
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea; Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea. Electronic address: sgh63@kcch.re.kr.
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D046988:Proteasome Endopeptidase Complex; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C092282:PSMC5 protein, human; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: Akt-Mdm2 pathway; H460 cancer cells; PSMC5; Radiosensitivity biomarker; p21