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

Wei Wen Liu, Shih Yu Chen, Chia Hsien Cheng, Hwai-Jong Cheng, Pei Hsin Huang

Research output: Contribution to journalArticle

3 Scopus citations

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 ofthedeveloping 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.

Original languageEnglish (US)
Pages (from-to)166-179
Number of pages14
JournalCell Reports
Volume9
Issue number1
DOIs
StatePublished - Oct 9 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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