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

M. K. Houseweart, A. Vilaythong, Xiao-Ming Yin, B. Turk, J. L. Noebels, R. M. Myers

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 2003
Externally publishedYes

Fingerprint

Progressive Myoclonic Epilepsy
Cathepsins
Apoptosis
Peptide Hydrolases
Cystatin B
Caspases
Cytochromes c
Breeding

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

  • Cell Biology

Cite this

Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1). / Houseweart, M. K.; Vilaythong, A.; Yin, Xiao-Ming; Turk, B.; Noebels, J. L.; Myers, R. M.

In: Cell Death and Differentiation, Vol. 10, No. 12, 12.2003, p. 1329-1335.

Research output: Contribution to journalArticle

Houseweart, M. K. ; Vilaythong, A. ; Yin, Xiao-Ming ; Turk, B. ; Noebels, J. L. ; Myers, R. M. / Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1). In: Cell Death and Differentiation. 2003 ; Vol. 10, No. 12. pp. 1329-1335.
@article{59c4a6652f4043eaa94832c169fa1a06,
title = "Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1)",
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.",
keywords = "Apoptosis, Ataxia, Bid, Cathepsin, Cell death, Cerebellum, Cystatin B, EPM1, Granule cell, Lysosome, Progressive myoclonus epilepsy, Stefin B, Unverricht-Lundborg",
author = "Houseweart, {M. K.} and A. Vilaythong and Xiao-Ming Yin and B. Turk and Noebels, {J. L.} and Myers, {R. M.}",
year = "2003",
month = "12",
doi = "10.1038/sj.cdd.4401309",
language = "English (US)",
volume = "10",
pages = "1329--1335",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1)

AU - Houseweart, M. K.

AU - Vilaythong, A.

AU - Yin, Xiao-Ming

AU - Turk, B.

AU - Noebels, J. L.

AU - Myers, R. M.

PY - 2003/12

Y1 - 2003/12

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Ataxia

KW - Bid

KW - Cathepsin

KW - Cell death

KW - Cerebellum

KW - Cystatin B

KW - EPM1

KW - Granule cell

KW - Lysosome

KW - Progressive myoclonus epilepsy

KW - Stefin B

KW - Unverricht-Lundborg

UR - http://www.scopus.com/inward/record.url?scp=0348038755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0348038755&partnerID=8YFLogxK

U2 - 10.1038/sj.cdd.4401309

DO - 10.1038/sj.cdd.4401309

M3 - Article

VL - 10

SP - 1329

EP - 1335

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 12

ER -