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Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules

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Abstract

Caspase-8 can trigger cell death following prodomain-mediated recruitment to the ‘death-inducing signaling complex.’ The prodomain consists of two death effector domain (DED) motifs that undergo homotypic interactions within the cell. Aside from mediating recruitment of procaspase-8, the prodomains have also been implicated in regulating cell survival, proliferation, death, senescence, differentiation, and substrate attachment. Here, we perform the initial characterization of a novel isoform of caspase-8, designated caspase-8 isoform 6 (Casp-8.6), which encodes both prodomain DEDs followed by a unique C-terminal tail. Casp-8.6 is detected in cells of the hematopoietic compartment as well as several other tissues. When Casp-8.6 expression is reconstituted in caspase-8-deficient cells, Casp-8.6 does not significantly impact cellular proliferation, contrasting with our previous results using a domain-defined ‘DED-only’ construct that lacks the C-terminal tail. Like the DED-only construct, Casp-8.6 also robustly forms ‘death effector’ filaments, but in contrast to the DED construct, it does not exhibit a dependence upon intact microtubules to scaffold filament formation. Both types of death effector filaments promote apoptosis when expressed in the presence of full length caspase-8 (isoform 1). Together, the results implicate Casp-8.6 as a new physiological modulator of apoptosis.

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Authors and Affiliations

  1. Moores UCSD Cancer Center, 3855, Health Sciences Drive, La Jolla, CA, 92039-0803, USA

    Robert T. Yuan, Shanique Young, Jesse Liang, Michael C. Schmid, Ainhoa Mielgo & Dwayne G. Stupack

  2. Warren College, University of California, San Diego, California, USA

    Robert T. Yuan

  3. Biomedical Sciences Graduate Training Program, University of California, San Diego, California, USA

    Shanique Young

  4. Department of Reproductive Medicine, San Diego School of Medicine, University of California, San Diego, California, USA

    Dwayne G. Stupack

Authors
  1. Robert T. Yuan
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  2. Shanique Young
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  3. Jesse Liang
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  4. Michael C. Schmid
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  5. Ainhoa Mielgo
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  6. Dwayne G. Stupack
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Corresponding author

Correspondence to Dwayne G. Stupack.

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Yuan, R.T., Young, S., Liang, J. et al. Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules. Apoptosis 17, 229–235 (2012). https://doi.org/10.1007/s10495-011-0677-y

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  • DOI: https://doi.org/10.1007/s10495-011-0677-y

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