title: Blm-s, a BH3-only protein enriched in postmitotic immature neurons, is transcriptionally upregulated by p53 during DNA damage.
abstract: Programmed cell death is a pivotal process that regulates neuronal number during development. Key regulators of this process are members of the BCL-2 family. Using mRNA differential display, we identified a Bcl-2 family gene, Blm-s (Bcl-2-like molecule, short form), enriched in postmitotic neurons of the developing cerebral cortex. BLM-s functions as a BH3-only apoptosis sensitizer/derepressor and causes BAX-dependent mitochondria-mediated apoptosis by selectively binding to prosurvival BCL-2 or MCL-1. When challenged with γ-irradiation that produces DNA double-strand breaks (DSBs), Blm-s is transcriptionally upregulated in postmitotic immature neurons with concurrently increased apoptosis. RNAi-mediated depletion of Blm-s protects immature neurons from irradiation-induced apoptosis. Furthermore, Blm-s is a direct target gene of p53 and AP1 via the ataxia telangiectasia mutated (ATM)- and c-Jun N-terminal kinase (JNK)-signaling pathways activated by DSBs. Thus, BLM-s is likely an apoptosis sensor activated by DSBs accumulating in postmitotic immature neurons.
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Physiology and Behavior, Department of Pathology and Laboratory Medicine, and Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA.
authors.forename: Shih-Yu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Neurobiology, Physiology and Behavior, Department of Pathology and Laboratory Medicine, and Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA. Electronic address: hjcheng@ucdavis.edu.
authors.forename: Hwai-Jong
authors.initials: HJ
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan. Electronic address: phhuang@ntu.edu.tw.
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D016923:Cell Death; D004249:DNA Damage; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015398:Signal Transduction; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D016159:Tumor Suppressor Protein p53