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Cell Rep. 2014 Oct 9;9(1):166-179. doi: 10.1016/j.celrep.2014.08.050. Epub 2014 Sep 25.

Blm-s, a BH3-only protein enriched in postmitotic immature neurons, is transcriptionally upregulated by p53 during DNA damage.

Author information

1
Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
2
Department of Neurobiology, Physiology and Behavior, Department of Pathology and Laboratory Medicine, and Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA.
3
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
4
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.
5
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.

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.

PMID:
25263558
DOI:
10.1016/j.celrep.2014.08.050
[Indexed for MEDLINE]
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