Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Cell Biol. 151 (5): 951-960

Copyright © 2000 by the Rockefeller University Press.


Original Article

Caspases Disrupt the Nuclear-Cytoplasmic Barrier

Lavina Faleiroa,b, and Yuri Lazebnika

a Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724
b Molecular and Cell Biology Graduate Program, State University of New York at Stony Brook, Stony Brook, New York 11733
Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724.(516) 367 8461(516) 367 8363

Abstract: During apoptosis, caspases, a family of proteases, disassemble a cell by cleaving a set of proteins. Caspase-3 plays a major role in the disassembly of the nucleus by processing several nuclear substrates. The question is how caspase-3, which is usually cytoplasmic, gains access to its nuclear targets. It was suggested that caspase-3 is actively transported to the nucleus through the nuclear pores. We found that caspase-9, which is activated earlier than caspase-3, directly or indirectly inactivates nuclear transport and increases the diffusion limit of the nuclear pores. This increase allows caspase-3 and other molecules that could not pass through the nuclear pores in living cells to enter or leave the nucleus during apoptosis by diffusion. Hence, caspase-9 contributes to cell disassembly by disrupting the nuclear-cytoplasmic barrier.

Key Words: apoptosis • caspases • nuclear transport • nuclear pores



Abbreviations used in this paper: C9DN, caspase-9 dominant-negative mutant; DAPI, 4'6-diamidino-2-phenylindole; GFP, green fluorescent protein; NLS, nuclear localization signal.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells.
R. van Wielink, M. M. Harmsen, D. E. Martens, B. P. H. Peeters, R. H. Wijffels, and R. J. M. Moormann (2012)
J. Virol. 86, 12341-12350
   Abstract »    Full Text »    PDF »
Apoptosis signaling in influenza virus propagation, innate host defense, and lung injury.
S. Herold, S. Ludwig, S. Pleschka, and T. Wolff (2012)
J. Leukoc. Biol. 92, 75-82
   Abstract »    Full Text »    PDF »
Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens.
V. A. Meliopoulos, L. E. Andersen, K. F. Birrer, K. J. Simpson, J. W. Lowenthal, A. G. D. Bean, J. Stambas, C. R. Stewart, S. M. Tompkins, V. W. van Beusechem, et al. (2012)
FASEB J 26, 1372-1386
   Abstract »    Full Text »    PDF »
Dissociation of chicken blastoderm for examination of apoptosis and necrosis by flow cytometry.
J. A. Hamidu, A. M. Rieger, G. M. Fasenko, and D. R. Barreda (2010)
Poultry Science 89, 901-909
   Abstract »    Full Text »    PDF »
Interactions between Viral and Prokaryotic Pathogens in a Mixed Infection with Cardiovirus and Mycoplasma.
P. V. Lidsky, L. I. Romanova, M. S. Kolesnikova, M. V. Bardina, E. V. Khitrina, S. V. Hato, F. J. M. van Kuppeveld, and V. I. Agol (2009)
J. Virol. 83, 9940-9951
   Abstract »    Full Text »    PDF »
Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution.
E. Reytor, J. Perez-Miguelsanz, L. Alvarez, D. Perez-Sala, and M. A. Pajares (2009)
FASEB J 23, 3347-3360
   Abstract »    Full Text »    PDF »
Targeting cell signalling pathways to fight the flu: towards a paradigm change in anti-influenza therapy.
S. Ludwig (2009)
J. Antimicrob. Chemother. 64, 1-4
   Abstract »    Full Text »    PDF »
Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase.
D. K. Moss, A. Wilde, and J. D. Lane (2009)
J. Cell Sci. 122, 644-655
   Abstract »    Full Text »    PDF »
Initiation of Programmed Cell Death in Self-Incompatibility: Role for Cytoskeleton Modifications and Several Caspase-Like Activities.
M. Bosch, N. S. Poulter, S. Vatovec, and V. E. Franklin-Tong (2008)
Mol Plant 1, 879-887
   Abstract »    Full Text »    PDF »
Apoptosis leads to a degradation of vital components of active nuclear transport and a dissociation of the nuclear lamina.
A. Kramer, I. Liashkovich, H. Oberleithner, S. Ludwig, I. Mazur, and V. Shahin (2008)
PNAS 105, 11236-11241
   Abstract »    Full Text »    PDF »
Temporal and spatial activation of caspase-like enzymes induced by self-incompatibility in Papaver pollen.
M. Bosch and V. E. Franklin-Tong (2007)
PNAS 104, 18327-18332
   Abstract »    Full Text »    PDF »
Geranylgeranylation but Not GTP Loading Determines Rho Migratory Function in T Cells.
S. Waiczies, I. Bendix, T. Prozorovski, M. Ratner, I. Nazarenko, C. F. Pfueller, A. U. Brandt, J. Herz, S. Brocke, O. Ullrich, et al. (2007)
J. Immunol. 179, 6024-6032
   Abstract »    Full Text »    PDF »
Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells.
M. Yuneva, N. Zamboni, P. Oefner, R. Sachidanandam, and Y. Lazebnik (2007)
J. Cell Biol. 178, 93-105
   Abstract »    Full Text »    PDF »
The extracellular release of HMGB1 during apoptotic cell death.
C. W. Bell, W. Jiang, C. F. Reich III, and D. S. Pisetsky (2006)
Am J Physiol Cell Physiol 291, C1318-C1325
   Abstract »    Full Text »    PDF »
Overexpression of caspase-3s splice variant in locally advanced breast carcinoma is associated with poor response to neoadjuvant chemotherapy..
F. Vegran, R. Boidot, C. Oudin, J.-M. Riedinger, F. Bonnetain, and S. Lizard-Nacol (2006)
Clin. Cancer Res. 12, 5794-5800
   Abstract »    Full Text »    PDF »
Dysregulated Human Myeloid Nuclear Differentiation Antigen Expression in Myelodysplastic Syndromes: Evidence for a Role in Apoptosis..
R. C. Briggs, K. E. Shults, L. A. Flye, S. A. McClintock-Treep, M. H. Jagasia, S. A. Goodman, F. I. Boulos, J. W. Jacobberger, G. T. Stelzer, and D. R. Head (2006)
Cancer Res. 66, 4645-4651
   Abstract »    Full Text »    PDF »
Nucleocytoplasmic Traffic Disorder Induced by Cardioviruses.
P. V. Lidsky, S. Hato, M. V. Bardina, A. G. Aminev, A. C. Palmenberg, E. V. Sheval, V. Y. Polyakov, F. J. M. van Kuppeveld, and V. I. Agol (2006)
J. Virol. 80, 2705-2717
   Abstract »    Full Text »    PDF »
Caspases Target Only Two Architectural Components within the Core Structure of the Nuclear Pore Complex.
M. Patre, A. Tabbert, D. Hermann, H. Walczak, H.-R. Rackwitz, V. C. Cordes, and E. Ferrando-May (2006)
J. Biol. Chem. 281, 1296-1304
   Abstract »    Full Text »    PDF »
A-Kinase-Anchoring Protein 95 Functions as a Potential Carrier for the Nuclear Translocation of Active Caspase 3 through an Enzyme-Substrate-Like Association.
S. Kamada, U. Kikkawa, Y. Tsujimoto, and T. Hunter (2005)
Mol. Cell. Biol. 25, 9469-9477
   Abstract »    Full Text »    PDF »
Myocyte apoptosis in heart failure.
V. P.M. van Empel, A. T.A. Bertrand, L. Hofstra, H. J. Crijns, P. A. Doevendans, and L. J. De Windt (2005)
Cardiovasc Res 67, 21-29
   Abstract »    Full Text »    PDF »
Cleavage at the Carboxyl-Terminus of Ku80 during Apoptosis in Human Jurkat T Cells.
M. Kato, T. Nonaka, and S. Imajoh-Ohmi (2005)
J. Biochem. 137, 685-692
   Abstract »    Full Text »    PDF »
Nuclear Translocation of Caspase-3 Is Dependent on Its Proteolytic Activation and Recognition of a Substrate-like Protein(s).
S. Kamada, U. Kikkawa, Y. Tsujimoto, and T. Hunter (2005)
J. Biol. Chem. 280, 857-860
   Abstract »    Full Text »    PDF »
Contrasting nuclear dynamics of the caspase-activated DNase (CAD) in dividing and apoptotic cells.
D. Lechardeur, M. Xu, and G. L. Lukacs (2004)
J. Cell Biol. 167, 851-862
   Abstract »    Full Text »    PDF »
Components of the Cell Death Machine and Drug Sensitivity of the National Cancer Institute Cell Line Panel.
P. A. Svingen, D. Loegering, J. Rodriquez, X. W. Meng, P. W. Mesner Jr., S. Holbeck, A. Monks, S. Krajewski, D. A. Scudiero, E. A. Sausville, et al. (2004)
Clin. Cancer Res. 10, 6807-6820
   Abstract »    Full Text »    PDF »
Bidirectional Increase in Permeability of Nuclear Envelope upon Poliovirus Infection and Accompanying Alterations of Nuclear Pores.
G. A. Belov, P. V. Lidsky, O. V. Mikitas, D. Egger, K. A. Lukyanov, K. Bienz, and V. I. Agol (2004)
J. Virol. 78, 10166-10177
   Abstract »    Full Text »    PDF »
Nucleosomes Are Exposed at the Cell Surface in Apoptosis.
M. Radic, T. Marion, and M. Monestier (2004)
J. Immunol. 172, 6692-6700
   Abstract »    Full Text »    PDF »
Ricin Triggers Apoptotic Morphological Changes through Caspase-3 Cleavage of BAT3.
Y.-H. Wu, S.-F. Shih, and J.-Y. Lin (2004)
J. Biol. Chem. 279, 19264-19275
   Abstract »    Full Text »    PDF »
On-Line Monitoring of Apoptosis in Insulin-Secreting Cells.
M. Kohler, S. V. Zaitsev, I. I. Zaitseva, B. Leibiger, I. B. Leibiger, M. Turunen, I. L. Kapelioukh, L. Bakkman, I. B. Appelskog, J. Boutet de Monvel, et al. (2003)
Diabetes 52, 2943-2950
   Abstract »    Full Text »    PDF »
Human Caspase-7 Activity and Regulation by Its N-terminal Peptide.
J.-B. Denault and G. S. Salvesen (2003)
J. Biol. Chem. 278, 34042-34050
   Abstract »    Full Text »    PDF »
Caspase 3 activation is essential for efficient influenza virus propagation.
W. J. Wurzer, O. Planz, C. Ehrhardt, M. Giner, T. Silberzahn, S. Pleschka, and S. Ludwig (2003)
EMBO J. 22, 2717-2728
   Abstract »    Full Text »    PDF »
Mitochondrially Localized Active Caspase-9 and Caspase-3 Result Mostly from Translocation from the Cytosol and Partly from Caspase-mediated Activation in the Organelle. LACK OF EVIDENCE FOR Apaf-1-MEDIATED PROCASPASE-9 ACTIVATION IN THE MITOCHONDRIA.
D. Chandra and D. G. Tang (2003)
J. Biol. Chem. 278, 17408-17420
   Abstract »    Full Text »    PDF »
Role of Caspases, Bid, and p53 in the Apoptotic Response Triggered by Histone Deacetylase Inhibitors Trichostatin-A (TSA) and Suberoylanilide Hydroxamic Acid (SAHA).
C. Henderson, M. Mizzau, G. Paroni, R. Maestro, C. Schneider, and C. Brancolini (2003)
J. Biol. Chem. 278, 12579-12589
   Abstract »    Full Text »    PDF »
Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects.
K. Takemoto, T. Nagai, A. Miyawaki, and M. Miura (2003)
J. Cell Biol. 160, 235-243
   Abstract »    Full Text »    PDF »
The Major Apoptotic Pathway Activated and Suppressed by Poliovirus.
G. A. Belov, L. I. Romanova, E. A. Tolskaya, M. S. Kolesnikova, Y. A. Lazebnik, and V. I. Agol (2003)
J. Virol. 77, 45-56
   Abstract »    Full Text »    PDF »
Pathological and Therapeutic Significance of Cellular Invasion by Proteus mirabilis in an Enterocystoplasty Infection Stone Model.
R. B. Mathoera, D. J. Kok, C. M. Verduin, and R. J. M. Nijman (2002)
Infect. Immun. 70, 7022-7032
   Abstract »    Full Text »    PDF »
A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis.
R. Chiu, L. Novikov, S. Mukherjee, and D. Shields (2002)
J. Cell Biol. 159, 637-648
   Abstract »    Full Text »    PDF »
Polypyrimidine Tract-binding Proteins Are Cleaved by Caspase-3 during Apoptosis.
S. H. Back, S. Shin, and S. K. Jang (2002)
J. Biol. Chem. 277, 27200-27209
   Abstract »    Full Text »    PDF »
Single-cell Fluorescence Resonance Energy Transfer Analysis Demonstrates That Caspase Activation during Apoptosis Is a Rapid Process. ROLE OF CASPASE-3.
M. Rehm, H. Dussmann, R. U. Janicke, J. M. Tavare, D. Kogel, and J. H. M. Prehn (2002)
J. Biol. Chem. 277, 24506-24514
   Abstract »    Full Text »    PDF »
Infection of Glioma Cells with Sindbis Virus Induces Selective Activation and Tyrosine Phosphorylation of Protein Kinase C delta . IMPLICATIONS FOR SINDBIS VIRUS-INDUCED APOPTOSIS.
A. Zrachia, M. Dobroslav, M. Blass, G. Kazimirsky, I. Kronfeld, P. M. Blumberg, D. Kobiler, S. Lustig, and C. Brodie (2002)
J. Biol. Chem. 277, 23693-23701
   Abstract »    Full Text »    PDF »
Caspase Proteolysis of the Cohesin Component RAD21 Promotes Apoptosis.
F. Chen, M. Kamradt, M. Mulcahy, Y. Byun, H. Xu, M. J. McKay, and V. L. Cryns (2002)
J. Biol. Chem. 277, 16775-16781
   Abstract »    Full Text »    PDF »
Caspase-2 Can Trigger Cytochrome c Release and Apoptosis from the Nucleus.
G. Paroni, C. Henderson, C. Schneider, and C. Brancolini (2002)
J. Biol. Chem. 277, 15147-15161
   Abstract »    Full Text »    PDF »
Prolonged Nuclear Retention of Activated Extracellular Signal-regulated Protein Kinase Promotes Cell Death Generated by Oxidative Toxicity or Proteasome Inhibition in a Neuronal Cell Line.
M. Stanciu and D. B. DeFranco (2002)
J. Biol. Chem. 277, 4010-4017
   Abstract »    Full Text »    PDF »
Lack of Correlation between Caspase Activation and Caspase Activity Assays in Paclitaxel-treated MCF-7 Breast Cancer Cells.
T. J. Kottke, A. L. Blajeski, X. W. Meng, P. A. Svingen, S. Ruchaud, P. W. Mesner Jr., S. A. Boerner, K. Samejima, N. V. Henriquez, T. J. Chilcote, et al. (2002)
J. Biol. Chem. 277, 804-815
   Abstract »    Full Text »
Tyrosine Phosphorylation of Protein Kinase C{delta} Is Essential for Its Apoptotic Effect in Response to Etoposide.
M. Blass, I. Kronfeld, G. Kazimirsky, P. M. Blumberg, and C. Brodie (2002)
Mol. Cell. Biol. 22, 182-195
   Abstract »    Full Text »    PDF »
Sequential degradation of proteins from the nuclear envelope during apoptosis.
M. Kihlmark, G. Imreh, and E. Hallberg (2001)
J. Cell Sci. 114, 3643-3653
   Abstract »    Full Text »    PDF »
Characterization of a Novel Isoform of Caspase-9 That Inhibits Apoptosis.
J. M. Angelastro, N. Y. Moon, D. X. Liu, A.-S. Yang, L. A. Greene, and T. F. Franke (2001)
J. Biol. Chem. 276, 12190-12200
   Abstract »    Full Text »    PDF »
Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes.
S. B. Bratton, G. Walker, S. M. Srinivasula, X.-M. Sun, M. Butterworth, E. S. Alnemri, and G. M. Cohen (2001)
EMBO J. 20, 998-1009
   Abstract »    Full Text »    PDF »
Characterization of a Novel Isoform of Caspase-9 That Inhibits Apoptosis.
J. M. Angelastro, N. Y. Moon, D. X. Liu, A.-S. Yang, L. A. Greene, and T. F. Franke (2001)
J. Biol. Chem. 276, 12190-12200
   Abstract »    Full Text »    PDF »
Caspase-2-induced Apoptosis Is Dependent on Caspase-9, but Its Processing during UV- or Tumor Necrosis Factor-dependent Cell Death Requires Caspase-3.
G. Paroni, C. Henderson, C. Schneider, and C. Brancolini (2001)
J. Biol. Chem. 276, 21907-21915
   Abstract »    Full Text »    PDF »
The Adapter Protein Apoptotic Protease-activating Factor-1 (Apaf-1) Is Proteolytically Processed during Apoptosis.
K. Lauber, H. A. E. Appel, S. F. Schlosser, M. Gregor, K. Schulze-Osthoff, and S. Wesselborg (2001)
J. Biol. Chem. 276, 29772-29781
   Abstract »    Full Text »    PDF »
Proapoptotic Stimuli Induce Nuclear Accumulation of Glycogen Synthase Kinase-3beta.
G. N. Bijur and R. S. Jope (2001)
J. Biol. Chem. 276, 37436-37442
   Abstract »    Full Text »    PDF »
NF-kappa B Activation Mediates Doxorubicin-induced Cell Death in N-type Neuroblastoma Cells.
X. Bian, L. M. McAllister-Lucas, F. Shao, K. R. Schumacher, Z. Feng, A. G. Porter, V. P. Castle, and A. W. Opipari Jr. (2001)
J. Biol. Chem. 276, 48921-48929
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882