title: Ubiquitinated sirtuin 1 (SIRT1) function is modulated during DNA damage-induced cell death and survival.
abstract: Downstream signaling of physiological and pathological cell responses depends on post-translational modification such as ubiquitination. The mechanisms regulating downstream DNA damage response (DDR) signaling are not completely elucidated. Sirtuin 1 (SIRT1), the founding member of Class III histone deacetylases, regulates multiple steps in DDR and is closely associated with many physiological and pathological processes. However, the role of post-translational modification or ubiquitination of SIRT1 during DDR is unclear. We show that SIRT1 is dynamically and distinctly ubiquitinated in response to DNA damage. SIRT1 was ubiquitinated by the MDM2 E3 ligase in vitro and in vivo. SIRT1 ubiquitination under normal conditions had no effect on its enzymatic activity or rate of degradation; hypo-ubiquitination, however, reduced SIRT1 nuclear localization. Ubiquitination of SIRT1 affected its function in cell death and survival in response to DNA damage. Our results suggest that ubiquitination is required for SIRT1 function during DDR.
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Lirong
authors: L
authors: Peng
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Zhigang
authors: Z
authors: Yuan
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Yixuan
authors: Y
authors: Li
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Hongbo
authors: H
authors: Ling
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Victoria
authors: V
authors: Izumi
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Bin
authors: B
authors: Fang
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Kenji
authors: K
authors: Fukasawa
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: John
authors: J
authors: Koomen
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors: Jiandong
authors: J
authors: Chen
authors: From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 ed.seto@moffitt.org.
authors: Edward
authors: E
authors: Seto
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D004249:DNA Damage; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D017931:DNA Primers; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Deubiquitylation (Deubiquitination); Histone Deacetylase (HDAC); Post-translational Modification (PTM); Sirtuin; Ubiquitylation (Ubiquitination)