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Caspase-8-mediated PAR-4 cleavage is required for TNFα-induced apoptosis.

Publication ,  Journal Article
Treude, F; Kappes, F; Fahrenkamp, D; Müller-Newen, G; Dajas-Bailador, F; Krämer, OH; Lüscher, B; Hartkamp, J
Published in: Oncotarget
May 2014

The tumor suppressor protein prostate apoptosis response-4 (PAR-4) is silenced in a subset of human cancers and its down-regulation serves as a mechanism for cancer cell survival following chemotherapy. PAR-4 re-expression selectively causes apoptosis in cancer cells but how its pro-apoptotic functions are controlled and executed precisely is currently unknown. We demonstrate here that UV-induced apoptosis results in a rapid caspase-dependent PAR-4 cleavage at EEPD131G, a sequence that was preferentially recognized by caspase-8. To investigate the effect on cell growth for this cleavage event we established stable cell lines that express wild-type-PAR-4 or the caspase cleavage resistant mutant PAR-4 D131G under the control of a doxycycline-inducible promoter. Induction of the wild-type protein but not the mutant interfered with cell proliferation, predominantly through induction of apoptosis. We further demonstrate that TNFα-induced apoptosis leads to caspase-8-dependent PAR-4-cleavage followed by nuclear accumulation of the C-terminal PAR-4 (132-340) fragment, which then induces apoptosis. Taken together, our results indicate that the mechanism by which PAR-4 orchestrates the apoptotic process requires cleavage by caspase-8.

Duke Scholars

Published In

Oncotarget

DOI

EISSN

1949-2553

ISSN

1949-2553

Publication Date

May 2014

Volume

5

Issue

10

Start / End Page

2988 / 2998

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Neoplasms
  • Mutagenesis, Site-Directed
  • Microscopy, Confocal
  • Humans
  • Fluorescent Antibody Technique
  • Cell Line, Tumor
  • Caspase 8
  • Apoptosis Regulatory Proteins
  • Apoptosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Treude, F., Kappes, F., Fahrenkamp, D., Müller-Newen, G., Dajas-Bailador, F., Krämer, O. H., … Hartkamp, J. (2014). Caspase-8-mediated PAR-4 cleavage is required for TNFα-induced apoptosis. Oncotarget, 5(10), 2988–2998. https://doi.org/10.18632/oncotarget.1634
Treude, Fabian, Ferdinand Kappes, Dirk Fahrenkamp, Gerhard Müller-Newen, Federico Dajas-Bailador, Oliver H. Krämer, Bernhard Lüscher, and Jörg Hartkamp. “Caspase-8-mediated PAR-4 cleavage is required for TNFα-induced apoptosis.Oncotarget 5, no. 10 (May 2014): 2988–98. https://doi.org/10.18632/oncotarget.1634.
Treude F, Kappes F, Fahrenkamp D, Müller-Newen G, Dajas-Bailador F, Krämer OH, et al. Caspase-8-mediated PAR-4 cleavage is required for TNFα-induced apoptosis. Oncotarget. 2014 May;5(10):2988–98.
Treude, Fabian, et al. “Caspase-8-mediated PAR-4 cleavage is required for TNFα-induced apoptosis.Oncotarget, vol. 5, no. 10, May 2014, pp. 2988–98. Epmc, doi:10.18632/oncotarget.1634.
Treude F, Kappes F, Fahrenkamp D, Müller-Newen G, Dajas-Bailador F, Krämer OH, Lüscher B, Hartkamp J. Caspase-8-mediated PAR-4 cleavage is required for TNFα-induced apoptosis. Oncotarget. 2014 May;5(10):2988–2998.

Published In

Oncotarget

DOI

EISSN

1949-2553

ISSN

1949-2553

Publication Date

May 2014

Volume

5

Issue

10

Start / End Page

2988 / 2998

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Neoplasms
  • Mutagenesis, Site-Directed
  • Microscopy, Confocal
  • Humans
  • Fluorescent Antibody Technique
  • Cell Line, Tumor
  • Caspase 8
  • Apoptosis Regulatory Proteins
  • Apoptosis