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Research Article

Modeling a Snap-Action, Variable-Delay Switch Controlling Extrinsic Cell Death

  • John G Albeck equal contributor,

    equal contributor Contributed equally to this work with: John G Albeck, John M Burke

    Affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America

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  • John M Burke equal contributor,

    equal contributor Contributed equally to this work with: John G Albeck, John M Burke

    Affiliations: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America, Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

    X
  • Sabrina L Spencer,

    Affiliations: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America, Computational and Systems Biology Initiative, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Douglas A Lauffenburger,

    Affiliations: Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, Computational and Systems Biology Initiative, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

    X
  • Peter K Sorger mail

    To whom correspondence should be addressed. E-mail: peter_sorger@hms.harvard.edu

    Affiliations: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America, Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Published: December 02, 2008
  • DOI: 10.1371/journal.pbio.0060299

Reader Comments (1)

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Role of caspase-mediated feedback in Td

Posted by plosbiology on 07 May 2009 at 22:28 GMT

Author: Peter Sorger
Position: Professor
Institution: Harvard Medical School
E-mail: peter_sorger@hms.harvard.edu
Submitted Date: December 08, 2008
Published Date: December 17, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

I am writing to expand on our analysis of the role caspase-6 plays during TRAIL-mediated apoptosis (Figure 10 of Albeck et al.). Evidence is growing that caspase-6 is not in fact able to cleave and activate caspase-8/10 as suggested by our cartoon (Figure 1), and thus, that our analysis of caspase-6 might not be biologically relevant . We are aware of this controversy and would like to point out that modeling actually pertains to an entire class of feedback processes in which effector caspases are able to activate additional initiator caspase molecules whether by caspase-6 or not. The analysis is relevant with regard to the processes that create an effective two-state apoptosis switch since it argues against an role for feedback regardless of its molecular mechanism. We welcome additional thoughts on this topic.

Competing interests declared: I am a senior author on the paper