Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1)

M. K. Houseweart, A. Vilaythong, X. M. Yin, B. Turk, J. L. Noebels, R. M. Myers

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Apoptosis can be mediated by mechanisms other than the traditional caspase-mediated cleavage cascade. There is growing recognition that alternative proteolytic enzymes such as the lysosomal cathepsin proteases can initiate or propagate proapoptotic signals, but it is currently unclear how cathepsins achieve these actions. Recent in vitro evidence suggests that cathepsins cleave the proapoptotic Bcl-2 family member Bid, thereby activating it and allowing it to induce the mitochondrial release of cytochrome c and subsequent apoptosis. We have tested this hypothesis in vivo by breeding mice that lack cathepsin inhibition (cystatin B-deficient mice) to Bid-deficient mice, to determine whether the apoptosis caused by cathepsins is dependent on Bid signaling. We found that cathepsins are still able to promote apoptosis even in the absence of Bid, indicating that these proteases mediate apoptosis via a different pathway, or that some other molecule can functionally substitute for Bid in this system.

Original languageEnglish (US)
Pages (from-to)1329-1335
Number of pages7
JournalCell Death and Differentiation
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2003

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Keywords

  • Apoptosis
  • Ataxia
  • Bid
  • Cathepsin
  • Cell death
  • Cerebellum
  • Cystatin B
  • EPM1
  • Granule cell
  • Lysosome
  • Progressive myoclonus epilepsy
  • Stefin B
  • Unverricht-Lundborg

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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