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Apoptosis effector mechanisms: A requiem performed in different keys

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Abstract

Apoptosis is the regulated form of cell death utilized by metazoans to remove unneeded, damaged, or potentially deleterious cells. Certain manifestations of apoptosis may be associated with the proteolytic activity of caspases. These changes are often held as hallmarks of apoptosis in dying cells. Consequently, many regard caspases as the central effectors or executioners of apoptosis. However, this “caspase-centric” paradigm of apoptotic cell death does not appear to be as universal as once believed. In fact, during apoptosis the efficacy of caspases may be highly dependent on the cytotoxic stimulus as well as genetic and epigenetic factors. An ever-increasing number of studies strongly suggest that there are effectors in addition to caspases, which are important in generating apoptotic signatures in dying cells. These seemingly caspase-independent effectors may represent evolutionarily redundant or failsafe mechanisms for apoptotic cell elimination. In this review, we will discuss the molecular regulation of caspases and various caspase-independent effectors of apoptosis, describe the potential context and/or limitations of these mechanisms, and explore why the understanding of these processes may have relevance in cancer where treatment is believed to engage apoptosis to destroy tumor cells.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmacy, Denver and Health Sciences Center, The University of Colorado, Denver, CO, 80262, USA

    N. Hail Jr.

  2. Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    B. Z. Carter, M. Konopleva & M. Andreeff M.D., Ph.D.

  3. Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, Unit 448, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    M. Andreeff M.D., Ph.D.

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  1. N. Hail Jr.
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  2. B. Z. Carter
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  3. M. Konopleva
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  4. M. Andreeff M.D., Ph.D.
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Correspondence to M. Andreeff M.D., Ph.D..

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Hail, N., Carter, B.Z., Konopleva, M. et al. Apoptosis effector mechanisms: A requiem performed in different keys. Apoptosis 11, 889–904 (2006). https://doi.org/10.1007/s10495-006-6712-8

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