RRP12 is a crucial nucleolar protein that regulates p53 activity in osteosarcoma cells.
RRP12 (ribosomal RNA processing 12 homolog), a nucleolar protein, plays important roles in cell cycle progression and the response to deoxyribonucleic acid (DNA) damage in yeast cells. However, its role has not been investigated in mammalian cells that possess p53, which has close functional association to nucleolus. We explored the role of RRP12 in nucleolar stress condition using an osteosarcoma cell line, U2OS. To induce DNA damage and nucleolar disruption, two cytotoxic drugs, doxorubicin and actinomycin D were used. Cytotoxic stress resulted nucleolar disruption induced cell cycle arrest and apoptosis in U2OS cells. However, RRP12 overexpression promoted resistance to cytotoxic stress. In contrast, RRP12 silencing enhanced susceptibility to cytotoxic stress. During drug treatment, p53 activity and cell death were suppressed by RRP12 overexpression but promoted by RRP12 silencing. This study demonstrated that RRP12 was crucial for cell survival during cytotoxic stress via the repression of p53 stability. Thus, targeting RRP12 may enhance chemotherapeutic effect in cancers.
Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 135-710, Korea.
Young Joon
YJ
Choi
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 135-710, Seoul, Korea.
Hye Won
HW
Lee
Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 135-710, Korea.
Yun Sun
YS
Lee
Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 135-710, Korea.
Da Mi
da M
Shim
Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 135-710, Korea. sungwseo@skku.edu.
Sung Wook
SW
Seo
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D009687:Nuclear Proteins; C000613872:RRP12 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003609:Dactinomycin; D004317:Doxorubicin
Actinomycin D; Doxorubicin; Nucleolar stress; Ribosomal RNA processing 12 homolog