title: SIRT4 regulates cancer cell survival and growth after stress.
abstract: Cellular stresses initiate well-coordinated signaling response pathways. As the proper regulation of stress is essential for cellular homeostasis, the defects of stress response pathways result in functional deficits and cell death. Although mitochondrial SIRT4 has been shown to be involved in cellular stress response and tumor suppression, its roles in survival and drug resistance of cancer cells are not well determined. Here we show that SIRT4 is a crucial regulator of the stress resistance of cancer cells. SIRT4 is highly induced by various cellular stresses and contributes to cell survival and growth after stresses. SIRT4 loss sensitizes cells to DNA damage or ER stress. Moreover, SIRT4 induction is required for tumorigenic transformation, as SIRT4 null cells are vulnerable to oncogene activation. Thus, these results suggest that SIRT4 has essential roles in stress resistance and may be an important therapeutic target for cancer treatment.
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea. Electronic address: smjeong@catholic.ac.kr.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Jeong
authors.affiliation: School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Sunsook
authors.initials: S
authors.lastname: Hwang
authors.affiliation: School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Rho Hyun
authors.initials: RH
authors.lastname: Seong
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D059865:Endoplasmic Reticulum Stress; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; C525357:SIRT4 protein, human; D037761:Sirtuins
keywords: Cancer; Replicative stress; SIRT4; Stress response