HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Posey, S. C. Articles by Bierer, B. E. Search for Related Content PubMed PubMed Citation Articles by Posey, S. C. Articles by Bierer, B. E.

J Biol Chem, Vol. 274, Issue 7, 4259-4265, February 12, 1999

Actin Stabilization by Jasplakinolide Enhances Apoptosis Induced by Cytokine Deprivation

S. Celeste Posey^§¶ and Barbara E. Bierer^¶**

From the  Department of Pediatric Oncology, Dana-Farber Cancer Institute, the ^§ Committee on Immunology, Division of Medical Sciences, and the ^** Department of Medicine, Harvard Medical School, Boston, Massachussets 02115 and the ^¶ NHLBI, National Institutes of Health, Bethesda, Maryland 20892

Participation of the actin cytoskeleton in the transduction of proliferative signals has been established through the use of compounds that disrupt the cytoskeleton. To address the possibility that actin also participates in the transduction of an apoptotic signal, we have studied the response of the murine interleukin 2 (IL-2)-dependent T cell line CTLL-20 to treatment with the actin-binding compound jasplakinolide upon IL-2 deprivation. Like phalloidin, jasplakinolide stabilizes F-actin and promotes actin polymerization. Treatment of CTLL-20 cells with jasplakinolide, in the presence or absence of recombinant human IL-2, altered actin morphology as assessed by confocal fluorescence microscopy. Jasplakinolide was not toxic to CTLL-20 cells, nor was apoptosis induced in the presence of exogenous recombinant human IL-2. However, actin stabilization at the time of IL-2 deprivation enhanced apoptosis by changing the time at which CTLL-20 cells committed to the apoptotic pathway. This effect of jasplakinolide correlated with its ability to stabilize polymerized actin, as treatment with a synthetic analog of jasplakinolide with a greatly reduced ability to bind actin, jasplakinolide B, did not enhance apoptosis. The enhancement occurred upstream of the induction of caspase-3-like activity and could be inhibited by the overexpression of the anti-apoptotic protein Bcl-x_L. These data suggest that the actin cytoskeleton plays an active role in modulating lymphocyte apoptosis induced by cytokine deprivation.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				M. E. Farah and D. C. Amberg Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast Mol. Biol. Cell, April 1, 2007; 18(4): 1359 - 1365. [Abstract] [Full Text] [PDF]

				N. Foger, L. Rangell, D. M. Danilenko, and A. C. Chan Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis. Science, August 11, 2006; 313(5788): 839 - 842. [Abstract] [Full Text] [PDF]

				S. G. Thomas, S. Huang, S. Li, C. J. Staiger, and V. E. Franklin-Tong Actin depolymerization is sufficient to induce programmed cell death in self-incompatible pollen J. Cell Biol., July 17, 2006; 174(2): 221 - 229. [Abstract] [Full Text] [PDF]

				J. Li, Q. Li, C. Xie, H. Zhou, Y. Wang, N. Zhang, H. Shao, S. C. Chan, X. Peng, S.-C. Lin, et al. {beta}-actin is required for mitochondria clustering and ROS generation in TNF-induced, caspase-independent cell death J. Cell Sci., September 15, 2004; 117(20): 4673 - 4680. [Abstract] [Full Text] [PDF]

				E. A. Papakonstanti and C. Stournaras Tumor Necrosis Factor-{alpha} Promotes Survival of Opossum Kidney Cells via Cdc42-induced Phospholipase C-{gamma}1 Activation and Actin Filament Redistribution Mol. Biol. Cell, March 1, 2004; 15(3): 1273 - 1286. [Abstract] [Full Text] [PDF]

				S.-J. Kim, S.-G. Hwang, I.-C. Kim, and J.-S. Chun Actin Cytoskeletal Architecture Regulates Nitric Oxide-induced Apoptosis, Dedifferentiation, and Cyclooxygenase-2 Expression in Articular Chondrocytes via Mitogen-activated Protein Kinase and Protein Kinase C Pathways J. Biol. Chem., October 24, 2003; 278(43): 42448 - 42456. [Abstract] [Full Text] [PDF]

				P. Widlak, O. Palyvoda, S. Kumala, and W. T. Garrard Modeling Apoptotic Chromatin Condensation in Normal Cell Nuclei. REQUIREMENT FOR INTRANUCLEAR MOBILITY AND ACTIN INVOLVEMENT J. Biol. Chem., June 7, 2002; 277(24): 21683 - 21690. [Abstract] [Full Text] [PDF]

				M. Kanzaki and J. E. Pessin Insulin-stimulated GLUT4 Translocation in Adipocytes Is Dependent upon Cortical Actin Remodeling J. Biol. Chem., November 2, 2001; 276(45): 42436 - 42444. [Abstract] [Full Text] [PDF]

				S. R. White, P. Williams, K. R. Wojcik, S. Sun, P. S. Hiemstra, K. F. Rabe, and D. R. Dorscheid Initiation of Apoptosis by Actin Cytoskeletal Derangement in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2001; 24(3): 282 - 294. [Abstract] [Full Text] [PDF]

				S. C. Posey, M. P. Martelli, T. Azuma, D. J. Kwiatkowski, and B. E. Bierer Failure of gelsolin overexpression to regulate lymphocyte apoptosis Blood, June 1, 2000; 95(11): 3483 - 3488. [Abstract] [Full Text] [PDF]

				M. C. Subauste, M. Von Herrath, V. Benard, C. E. Chamberlain, T.-H. Chuang, K. Chu, G. M. Bokoch, and K. M. Hahn Rho Family Proteins Modulate Rapid Apoptosis Induced by Cytotoxic T Lymphocytes and Fas J. Biol. Chem., March 24, 2000; 275(13): 9725 - 9733. [Abstract] [Full Text] [PDF]