Abstract
Caspase-8 performs initiatory functions during the induction of apoptosis through the extrinsic pathway. Apoptosis is a type of programmed cell death that plays an important role in regulating embryogenesis and maintaining homeostasis in the tissue of an adult organism, as well as differentiating and removing damaged cells. Dysregulation of the apoptosis mechanisms is associated with the pathogenesis and progression of a number of oncological and neurodegenerative diseases. Caspase-8 (also called СAP4, FLICE, MACH, MCH5) is one of two members of the death effector domain (DED)-containing caspases. Despite the fact that the role of caspase-8 in apoptosis has been well known since the mid 1990s, we are only now beginning to understand the subtle mechanisms of its activation and regulation in response to the activation of death receptors (DRs). In particular, it was demonstrated that the activation of caspase-8 requires the formation of specific oligomeric structures, which are named DED filaments. In this review, the recent data on the mechanisms of activating initiator caspase-8 in DED filaments are considered that allow us to better understand the subtle mechanisms of the initiation of the programmed cell death.
Similar content being viewed by others
REFERENCES
Krammer P.H., Arnold R., Lavrik I.N. 2007. Life and death in peripheral T cells. Nat. Rev. Immunol. 7, 532‒542.
Zamaraev A.V., Kopeina G.S., Zhivotovsky B., Lavrik I.N. 2015. Cell death controlling complexes and their potential therapeutic role. Cell Mol. Life Sci. 72, 505‒517.
Lavrik I., Golks A., Krammer P.H. 2005. Death receptor signaling. J. Cell Sci. 118, 265‒267.
Lavrik I.N., Golks A., Krammer P.H. 2005. Caspases: Pharmacological manipulation of cell death. J. Clin. Invest. 115, 2665‒2672.
Zamaraev A.V., Kopeina G.S., Prokhorova E.A., Zhivotovsky B., Lavrik I.N. 2017. Post-translational modification of caspases: The other side of apoptosis regulation. Trends Cell Biol. 27, 322‒339.
Golks A., Brenner D., Fritsch C., Krammer P.H., Lavrik I.N. 2005. c-FLIPR, a new regulator of death receptor-induced apoptosis. J. Biol. Chem. 280, 14507‒14513.
Lavrik I.N., Krammer P.H. 2012. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ. 19, 36‒41.
Aksenova V.I., Bylino O.V., Zhivotovsky B.D., Lavrik I.N. 2013. Caspase-2: What do we know today? Mol. Biol. (Moscow). 47 (2), 165–180.
Lavrik I.N. 2014. Systems biology of death receptor networks: live and let die. Cell Death Dis. 5, e1259.
Riess D., Lavrik I.N. 2010. Application o two-dimensional electrophoresis to studying the composition of the receptor complex formed on the CD45/Fas receptor. Acta Naturae. 2 (5), 102‒107.
Horn S., Hughes M.A., Schilling R., Sticht C., Tenev T., Ploesser M., Meier P., Sprick M.R., MacFarlane M., Leverkus M. 2017. Caspase-10 negatively regulates caspase-8-mediated cell death, switching the response to CD95L in favor of NF-kappaB activation and cell survival. Cell Rep. 19, 785‒797.
Lafont E., Kantari-Mimoun C., Draber P., De Miguel D., Hartwig T., Reichert M., Kupka S., Shimizu Y., Taraborrelli L., Spit M., Sprick M.R., Walczak H. 2017. The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death. EMBO J. 36, 1147‒1166.
Cullen S.P., Martin S.J. 2015. Fas and TRAIL 'death receptors’ as initiators of inflammation: Implications for cancer. Semin. Cell. Dev. Biol. 39, 26‒34.
Hoffmann J.C., Pappa A., Krammer P.H., Lavrik I.N. 2009. A new C-terminal cleavage product of procaspase-8, p30, defines an alternative pathway of procaspase-8 activation. Mol. Cell. Biol. 29, 4431‒4440.
Schleich K., Buchbinder J.H., Pietkiewicz S., Kahne T., Warnken U., Ozturk S., Schnolzer M., Naumann M., Krammer P.H., Lavrik I.N. 2016. Molecular architecture of the DED chains at the DISC: Regulation of procaspase-8 activation by short DED proteins c-FLIP and procaspase-8 prodomain. Cell Death Differ. 23, 681‒694.
Golks A., Brenner D., Schmitz I., Watzl C., Krueger A., Krammer P.H., Lavrik I.N. 2006. The role of CAP3 in CD95 signaling: New insights into the mechanism of procaspase-8 activation. Cell Death Differ. 13, 489‒498.
Lavrik I., Krueger A., Schmitz I., Baumann S., Weyd H., Krammer P.H., Kirchhoff S. 2003. The active caspase-8 heterotetramer is formed at the CD95 DISC. Cell Death Differ. 10, 144‒145.
Hughes M.A., Powley I.R., Jukes-Jones R., Horn S., Feoktistova M., Fairall L., Schwabe J.W., Leverkus M., Cain K., MacFarlane M. 2016. Co-operative and hierarchical binding of c-FLIP and caspase-8: A unified model defines how c-FLIP isoforms differentially control cell fate. Mol. Cell. 61, 834‒849.
Powley I.R., Hughes M.A., Cain K., MacFarlane M. 2016. Caspase-8 tyrosine-380 phosphorylation inhibits CD95 DISC function by preventing procaspase-8 maturation and cycling within the complex. Oncogene. 35, 5629‒5640.
Hughes M.A., Harper N., Butterworth M., Cain K., Cohen G.M., MacFarlane M. 2009. Reconstitution of the death-inducing signaling complex reveals a substrate switch that determines CD95-mediated death or survival. Mol. Cell. 35, 265‒279.
Schleich K., Warnken U., Fricker N., Ozturk S., Richter P., Kammerer K., Schnolzer M., Krammer P.H., Lavrik I.N. 2012. Stoichiometry of the CD95 death-inducing signaling complex: Experimental and modeling evidence for a death effector domain chain model. Mol. Cell. 47, 306‒319.
Dickens L.S., Boyd R.S., Jukes-Jones R., Hughes M.A., Robinson G.L., Fairall L., Schwabe J.W., Cain K., Macfarlane M. 2012. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol. Cell. 47, 291‒305.
Schleich K., Krammer P.H., Lavrik I.N. 2013. The chains of death: A new view on caspase-8 activation at the DISC. Cell Cycle. 12, 193‒194.
Fu T.M., Li Y., Lu A., Li Z., Vajjhala P.R., Cruz A.C., Srivastava D.B., DiMaio F., Penczek P.A., Siegel R.M., Stacey K.J., Egelman E.H., Wu H. 2016. Cryo-EM structure of caspase-8 tandem DED filament reveals assembly and regulation mechanisms of the death-inducing signaling complex. Mol. Cell. 64, 236‒250.
Ferrao R., Li J., Bergamin E., Wu H. 2012. Structural insights into the assembly of large oligomeric signalosomes in the Toll-like receptor-interleukin-1 receptor superfamily. Sci. Signal. 5, re3.
Singh N., Hassan A., Bose K. 2016. Molecular basis of death effector domain chain assembly and its role in caspase-8 activation. FASEB J. 30, 186‒200.
Wang L., Yang J.K., Kabaleeswaran V., Rice A.J., Cruz A.C., Park A.Y., Yin Q., Damko E., Jang S.B., Raunser S., Robinson C.V., Siegel R.M., Walz T., Wu H. 2010. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat. Struct. Mol. Biol. 17, 1324‒1329.
Bentele M., Lavrik I., Ulrich M., Stosser S., Heermann D.W., Kalthoff H., Krammer P.H., Eils R. 2004. Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis. J. Cell. Biol. 166, 839‒851.
Boege Y., Malehmir M., Healy M.E., Bettermann K., Lorentzen A., Vucur M., Ahuja A.K., Bohm F., Mertens J.C., Shimizu Y., Frick L., Remouchamps C., Mutreja K., Kähne T., Sundaravinayagam D., et al. 2017. A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development. Cancer Cell. 32, 342‒359, e310.
Sarhan J., Liu B.C., Muendlein H.I., Li P., Nilson R., Tang A.Y., Rongvaux A., Bunnell S.C., Shao F., Green D.R., Poltorak A. 2018. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. Proc. Natl. Acad. Sci. U. S. A. 115, E10888‒E10897.
Tenev T., Bianchi K., Darding M., Broemer M., Langlais C., Wallberg F., Zachariou A., Lopez J., MacFarlane M., Cain K., Meier P. 2011. The ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell. 43, 432‒448.
Funding
This work was supported by the Russian Foundation for Basic Research (grant no. 18-04-00207) and by the budget no. 0324-2019-0040.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
Additional information
Translated by A. Barkhash
Rights and permissions
About this article
Cite this article
Ivanisenko, N.V., Lavrik, I.N. Mechanisms of Procaspase-8 Activation in the Extrinsic Programmed Cell Death Pathway. Mol Biol 53, 732–738 (2019). https://doi.org/10.1134/S0026893319050091
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893319050091