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 Samejima, K. Articles by Earnshaw, W. C. Search for Related Content PubMed PubMed Citation Articles by Samejima, K. Articles by Earnshaw, W. C. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 7, 4335-4340, February 12, 1999

Caspase-mediated Cleavage of DNA Topoisomerase I at Unconventional Sites during Apoptosis

From the ^a Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, Scotland, United Kingdom, the ^b Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, ^c Athena Neurosciences, Inc., South San Francisco, California 94080, the ^h Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107-5541, the ^g Centre Hospitalier de l'Université Laval Research Center and Laval University, Sainte-Foy, Quebec G1V 4G2, Canada, and the ^d Biomolecular Structure Center and the Departments of ^e Biological Structure and ⁱ Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195

Previous studies have demonstrated that topoisomerase I is cleaved late during apoptosis, but have not identified the proteases responsible or examined the functional consequences of this cleavage. Here, we have shown that treatment of purified topoisomerase I with caspase-3 resulted in cleavage at DDVD¹⁴⁶Y and EEED¹⁷⁰G, whereas treatment with caspase-6 resulted in cleavage at PEDD¹²³G and EEED¹⁷⁰G. After treatment of Jurkat T lymphocytic leukemia cells with anti-Fas antibody or A549 lung cancer cells with topotecan, etoposide, or paclitaxel, the topoisomerase I fragment comigrated with the product that resulted from caspase-3 cleavage at DDVD¹⁴⁶Y. In contrast, two discrete topoisomerase I fragments that appeared to result from cleavage at DDVD¹⁴⁶Y and EEED¹⁷⁰G were observed after treatment of MDA-MB-468 breast cancer cells with paclitaxel. Topoisomerase I cleavage did not occur in apoptotic MCF-7 cells, which lack caspase-3. Cell fractionation and band depletion studies with the topoisomerase I poison topotecan revealed that the topoisomerase I fragment remains in proximity to the chromatin and retains the ability to bind to and cleave DNA. These observations indicate that topoisomerase I is a substrate of caspase-3 and possibly caspase-6, but is cleaved at sequences that differ from those ordinarily preferred by these enzymes, thereby providing a potential explanation why topoisomerase I cleavage lags behind that of classical caspase substrates such as poly(ADP-ribose) polymerase and lamin B₁.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				O. Sordet, A. Goldman, C. Redon, S. Solier, V. A. Rao, and Y. Pommier Topoisomerase I Requirement for Death Receptor-induced Apoptotic Nuclear Fission J. Biol. Chem., August 22, 2008; 283(34): 23200 - 23208. [Abstract] [Full Text] [PDF]

				G. Klaiman, T. L. Petzke, J. Hammond, and A. C. LeBlanc Targets of Caspase-6 Activity in Human Neurons and Alzheimer Disease Mol. Cell. Proteomics, August 1, 2008; 7(8): 1541 - 1555. [Abstract] [Full Text] [PDF]

				K. Sone, S. Nakagawa, K. Nakagawa, S. Takizawa, Y. Matsumoto, K. Nagasaka, T. Tsuruga, H. Hiraike, O. Hiraike-Wada, Y. Miyamoto, et al. hScrib, a human homologue of Drosophila neoplastic tumor suppressor, is a novel death substrate targeted by caspase during the process of apoptosis. Genes Cells, July 1, 2008; 13(7): 771 - 785. [Abstract] [Full Text] [PDF]

				M. Kato, T. Nonaka, and S. Imajoh-Ohmi Cleavage at the Carboxyl-Terminus of Ku80 during Apoptosis in Human Jurkat T Cells J. Biochem., June 1, 2005; 137(6): 685 - 692. [Abstract] [Full Text] [PDF]

				P. Q. Hu, N. Fertig, T. A. Medsger Jr, and T. M. Wright Molecular Recognition Patterns of Serum Anti-DNA Topoisomerase I Antibody in Systemic Sclerosis J. Immunol., August 15, 2004; 173(4): 2834 - 2841. [Abstract] [Full Text] [PDF]

				O. Sordet, Z. Liao, H. Liu, S. Antony, E. V. Stevens, G. Kohlhagen, H. Fu, and Y. Pommier Topoisomerase I-DNA Complexes Contribute to Arsenic Trioxide-induced Apoptosis J. Biol. Chem., August 6, 2004; 279(32): 33968 - 33975. [Abstract] [Full Text] [PDF]

				F. Chen, O. K. Arseven, and V. L. Cryns Proteolysis of the Mismatch Repair Protein MLH1 by Caspase-3 Promotes DNA Damage-induced Apoptosis J. Biol. Chem., June 25, 2004; 279(26): 27542 - 27548. [Abstract] [Full Text] [PDF]

				D. Mandal, V. Baudin-Creuza, A. Bhattacharyya, S. Pathak, J. Delaunay, M. Kundu, and J. Basu Caspase 3-mediated Proteolysis of the N-terminal Cytoplasmic Domain of the Human Erythroid Anion Exchanger 1 (Band 3) J. Biol. Chem., December 26, 2003; 278(52): 52551 - 52558. [Abstract] [Full Text] [PDF]

				J. Soret, M. Gabut, C. Dupon, G. Kohlhagen, J. Stevenin, Y. Pommier, and J. Tazi Altered Serine/Arginine-Rich Protein Phosphorylation and Exonic Enhancer-Dependent Splicing in Mammalian Cells Lacking Topoisomerase I Cancer Res., December 1, 2003; 63(23): 8203 - 8211. [Abstract] [Full Text] [PDF]

				B. Zhang, Y. Zhang, and E. Shacter Caspase 3-Mediated Inactivation of Rac GTPases Promotes Drug-Induced Apoptosis in Human Lymphoma Cells Mol. Cell. Biol., August 15, 2003; 23(16): 5716 - 5725. [Abstract] [Full Text] [PDF]

				N. Al-Molawi, V. A. Beardmore, M. J. Carter, G. E. N. Kass, and L. O. Roberts Caspase-mediated cleavage of the feline calicivirus capsid protein J. Gen. Virol., May 1, 2003; 84(5): 1237 - 1244. [Abstract] [Full Text] [PDF]

				M. Kamachi, T. M. Le, S. J. Kim, M. E. Geiger, P. Anderson, and P. J. Utz Human Autoimmune Sera as Molecular Probes for the Identification of an Autoantigen Kinase Signaling Pathway J. Exp. Med., November 4, 2002; 196(9): 1213 - 1226. [Abstract] [Full Text] [PDF]

				S. H. Back, S. Shin, and S. K. Jang Polypyrimidine Tract-binding Proteins Are Cleaved by Caspase-3 during Apoptosis J. Biol. Chem., July 19, 2002; 277(30): 27200 - 27209. [Abstract] [Full Text] [PDF]

				M. Huang, P. Kozlowski, M. Collins, Y. Wang, T. A. Haystead, and L. M. Graves Caspase-Dependent Cleavage of Carbamoyl Phosphate Synthetase II during Apoptosis Mol. Pharmacol., March 1, 2002; 61(3): 569 - 577. [Abstract] [Full Text] [PDF]

				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. Lack of Correlation between Caspase Activation and Caspase Activity Assays in Paclitaxel-treated MCF-7 Breast Cancer Cells J. Biol. Chem., January 4, 2002; 277(1): 804 - 815. [Abstract] [Full Text]

				O. Nyormoi, Z. Wang, D. Doan, M. Ruiz, D. McConkey, and M. Bar-Eli Transcription Factor AP-2{alpha} Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer Cells Mol. Cell. Biol., August 1, 2001; 21(15): 4856 - 4867. [Abstract] [Full Text] [PDF]

				X. Zhang and F. Kiechle Hoechst 33342-Induced Apoptosis is Associated with Decreased Immunoreactive Topoisomerase I and Topoisomerase I-DNA Complex Formation Ann. Clin. Lab. Sci., April 1, 2001; 31(2): 187 - 198. [Abstract] [Full Text] [PDF]

				C. Rampon, C. H. Jiang, H. Dong, Y.-P. Tang, D. J. Lockhart, P. G. Schultz, J. Z. Tsien, and Y. Hu Effects of environmental enrichment on gene expression in the brain PNAS, November 7, 2000; 97(23): 12880 - 12884. [Abstract] [Full Text] [PDF]

				A. H. Stegh, H. Herrmann, S. Lampel, D. Weisenberger, K. Andrä, M. Seper, G. Wiche, P. H. Krammer, and M. E. Peter Identification of the Cytolinker Plectin as a Major Early In Vivo Substrate for Caspase 8 during CD95- and Tumor Necrosis Factor Receptor-Mediated Apoptosis Mol. Cell. Biol., August 1, 2000; 20(15): 5665 - 5679. [Abstract] [Full Text]

				H.-J. Chen, C.-L. Hwong, C.-H. Wang, and J. Hwang Degradation of DNA Topoisomerase I by a Novel Trypsin-like Serine Protease in Proliferating Human T Lymphocytes J. Biol. Chem., April 21, 2000; 275(17): 13109 - 13117. [Abstract] [Full Text] [PDF]

				S. Y. Hsu and A. J. W. Hsueh Tissue-Specific Bcl-2 Protein Partners in Apoptosis: An Ovarian Paradigm Physiol Rev, April 1, 2000; 80(2): 593 - 614. [Abstract] [Full Text] [PDF]

				T. E. Witzig, M. Timm, M. Stenson, P. A. Svingen, and S. H. Kaufmann Induction of Apoptosis in Malignant B Cells by Phenylbutyrate or Phenylacetate in Combination with Chemotherapeutic Agents Clin. Cancer Res., February 1, 2000; 6(2): 681 - 692. [Abstract] [Full Text]

				J Gotzmann, S Vlcek, and R Foisner Caspase-mediated cleavage of the chromosome-binding domain of lamina-associated polypeptide 2 alpha J. Cell Sci., January 11, 2000; 113(21): 3769 - 3780. [Abstract] [PDF]

				K. Hishikawa, B. S. Oemar, F. C. Tanner, T. Nakaki, T. F. Luscher, and T. Fujii Connective Tissue Growth Factor Induces Apoptosis in Human Breast Cancer Cell Line MCF-7 J. Biol. Chem., December 24, 1999; 274(52): 37461 - 37466. [Abstract] [Full Text] [PDF]

				Y. Takeda, P. Caudell, G. Grady, G. Wang, A. Suwa, G. C. Sharp, W. S. Dynan, and J. A. Hardin Human RNA Helicase A Is a Lupus Autoantigen That Is Cleaved During Apoptosis J. Immunol., December 1, 1999; 163(11): 6269 - 6274. [Abstract] [Full Text] [PDF]

				G. Cutrona, N. Leanza, M. Ulivi, G. Melioli, V. L. Burgio, G. Mazzarello, G. Gabutti, S. Roncella, and M. Ferrarini Expression of CD10 by Human T Cells That Undergo Apoptosis Both In Vitro and In Vivo Blood, November 1, 1999; 94(9): 3067 - 3076. [Abstract] [Full Text] [PDF]

				K. Endo, E. Oki, V. Biedermann, H. Kojima, K. Yoshida, F.-J. Johannes, D. Kufe, and R. Datta Proteolytic Cleavage and Activation of Protein Kinase C {micro} by Caspase-3 in the Apoptotic Response of Cells to 1-beta -D-Arabinofuranosylcytosine and Other Genotoxic Agents J. Biol. Chem., June 9, 2000; 275(24): 18476 - 18481. [Abstract] [Full Text] [PDF]

				Y.-Y. Mo, C. Wang, and W. T. Beck A Novel Nuclear Localization Signal in Human DNA Topoisomerase I J. Biol. Chem., December 22, 2000; 275(52): 41107 - 41113. [Abstract] [Full Text] [PDF]

				E. B. Affar, M. Germain, E. Winstall, M. Vodenicharov, R. G. Shah, G. S. Salvesen, and G. G. Poirier Caspase-3-mediated Processing of Poly(ADP-ribose) Glycohydrolase during Apoptosis J. Biol. Chem., January 19, 2001; 276(4): 2935 - 2942. [Abstract] [Full Text] [PDF]

				E. A. Slee, C. Adrain, and S. J. Martin Executioner Caspase-3, -6, and -7 Perform Distinct, Non-redundant Roles during the Demolition Phase of Apoptosis J. Biol. Chem., March 2, 2001; 276(10): 7320 - 7326. [Abstract] [Full Text] [PDF]