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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • BH3 Interacting Domain Death Agonist Protein / metabolism*
  • Cell Death
  • DNA Damage*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Signal Transduction
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation


  • BH3 Interacting Domain Death Agonist Protein
  • Tumor Suppressor Protein p53

Associated data

  • GENBANK/DQ869383