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Autoproteolytic Activation of Pro-Caspases by Oligomerization

Yang, Xiaolu and Chang, Howard Y. and Baltimore, David (1998) Autoproteolytic Activation of Pro-Caspases by Oligomerization. Molecular Cell, 1 (2). pp. 319-325. ISSN 1097-2765. doi:10.1016/s1097-2765(00)80032-5.

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Initiation of apoptosis requires the conversion of pro-caspases to mature caspases. Here we show that oligomerization of pro-caspases is sufficient to induce proteolytic generation of mature caspase subunits and activation of their cell death activity. Deletion of the protein interaction motif DED from pro-caspase-8 greatly suppresses its apoptotic activity. Cell death activity can be restored by oligomerization of pro-caspase-8 protease domains by two heterologous inducible oligomerization systems. Induced oligomerization also activates the apoptotic activity of pro-caspase-1 but not pro-caspase-3. In vitro, oligomerization leads to pro-caspase processing to form the mature caspase subunits; this processing requires the intrinsic caspase activity of zymogens and proceeds via a novel order of cleavage events.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1998 Cell Press. Under an Elsevier user license. Received 18 November 1997, Revised 8 December 1997, Available online 11 April 2001. We thank Y. H. Li and P. Svec for excellent technical support. We are grateful to M. Gilman for the generous gift of AP1510. We thank Drs. E. S. Alnemri, D. V. Goeddel, M. J. Lenardo, J. Liu, Z. Luo, S. L. Schreiber, Z. Song, D. Xue, and J. Yuan for reagents and advice. We thank Dr. A. Hoffmann for help with in vitro translation, and A. J. Koleske, B. Horwitz, Z. Songyang, and other members of the Baltimore lab for valuable advice. X. Y. is a fellow of the Leukemia Society of America, and H. Y. C. is supported by the Medical Scientist Training Program at Harvard Medical School. D. B. is an American Cancer Society Research Professor. This work was supported by NIH grant CA51462.
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Leukemia Society of AmericaUNSPECIFIED
Harvard Medical SchoolUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20200422-150958515
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Official Citation:Xiaolu Yang, Howard Y Chang, David Baltimore, Autoproteolytic Activation of Pro-Caspases by Oligomerization, Molecular Cell, Volume 1, Issue 2, 1998, Pages 319-325, ISSN 1097-2765,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102725
Deposited By: George Porter
Deposited On:23 Apr 2020 19:41
Last Modified:16 Nov 2021 18:14

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