Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
August 2013 Volume 30 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August 2013 Volume 30 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Cleavage of bleomycin hydrolase by caspase-3 during apoptosis

  • Authors:
    • Yang Chen
    • Rong Xu
    • Jianguo Chen
    • Xiaoyu Li
    • Qiyang He
  • View Affiliations / Copyright

    Affiliations: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P.R. China
  • Pages: 939-944
    |
    Published online on: May 23, 2013
       https://doi.org/10.3892/or.2013.2484
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Chen J and Stubbe J: Bleomycins: towards better therapeutics. Nat Rev Cancer. 5:102–112. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Okamura Y, Nomoto S, Hayashi M, et al: Identification of the bleomycin hydrolase gene as a methylated tumor suppressor gene in hepatocellular carcinoma using a novel triple-combination array method. Cancer Lett. 312:150–157. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Towne CF, York IA, Watkin LB, Lazo JS and Rock KL: Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses. J Immunol. 178:6923–6930. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Suszynska J, Tisonczyk J, Lee HG, Smith MA and Jakubowski H: Reduced homocysteine-thiolactonase activity in Alzheimer’s disease. J Alzheimers Dis. 19:1177–1183. 2010.PubMed/NCBI

5 

Lefterov IM, Koldamova RP and Lazo JS: Human bleomycin hydrolase regulates the secretion of amyloid precursor protein. FASEB J. 14:1837–1847. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Zimny J, Sikora M, Guranowski A and Jakubowski H: Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase. J Biol Chem. 281:22485–22492. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Ratovitski T, Chighladze E, Waldron E, Hirschhorn RR and Ross CA: Cysteine proteases bleomycin hydrolase and cathepsin Z mediate N-terminal proteolysis and toxicity of mutant huntingtin. J Biol Chem. 286:12578–12589. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Kamata Y, Taniguchi A, Yamamoto M, Nomura J, Ishihara K, Takahara H, Hibino T and Takeda A: Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids. J Biol Chem. 284:12829–12836. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Ferrando AA, Pendás AM, Llano E, Velasco G, Lidereau R and López-Otín C: Gene characterization, promoter analysis, and chromosomal localization of human bleomycin hydrolase. J Biol Chem. 272:33298–33304. 1997. View Article : Google Scholar : PubMed/NCBI

10 

Ferrando AA, Velasco G, Campo E and Lopez-Otin C: Cloning and expression analysis of human bleomycin hydrolase, a cysteine proteinase involved in chemotherapy resistance. Cancer Res. 56:1746–1750. 1996.PubMed/NCBI

11 

Brömme D, Rossi AB, Smeekens SP, Anderson DC and Payan DG: Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization. Biochemistry. 35:6706–6714. 1996.PubMed/NCBI

12 

Montoya SE, Ferrell RE and Lazo JS: Genomic structure and genetic mapping of the human neutral cysteine protease bleomycin hydrolase. Cancer Res. 57:4191–4195. 1997.PubMed/NCBI

13 

Chen J, Chen Y and He Q: Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1. Int J Oncol. 41:2245–2252. 2012.PubMed/NCBI

14 

Lazo JS, Boland CJ and Schwartz PE: Bleomycin hydrolase activity and cytotoxicity in human tumors. Cancer Res. 42:4026–4031. 1982.PubMed/NCBI

15 

Schwartz DR, Homanics GE, Hoyt DG, Klein E, Abernethy J and Lazo JS: The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci USA. 96:4680–4685. 1999. View Article : Google Scholar : PubMed/NCBI

16 

De Haas EC, Zwart N, Meijer C, et al: Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer. J Clin Oncol. 26:1817–1823. 2008.PubMed/NCBI

17 

Timmer JC and Salvesen GS: Caspase substrates. Cell Death Differ. 214:66–72. 2007. View Article : Google Scholar

18 

Crawford ED and Wells JA: Caspase substrates and cellular remodeling. Annu Rev Biochem. 80:1055–1087. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Xu G, Cirilli M, Huang Y, Rich RL, Myszka DG and Wu H: Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex. Nature. 410:494–497. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Koldamova RP, Lefterov IM, DiSabella MT and Lazo JS: An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9. Mol Pharmacol. 54:954–961. 1998.PubMed/NCBI

21 

Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, et al: Global quantification of mammalian gene expression control. Nature. 473:337–342. 2011.

22 

Pei Z, Calmels TP, Creutz CE and Sebti SM: Yeast cysteine proteinase gene ycp1 induces resistance to bleomycin in mammalian cells. Mol Pharmacol. 48:676–681. 1995.PubMed/NCBI

23 

Montoya SE, Thiels E, Card JP and Lazo JS: Astrogliosis and behavioral changes in mice lacking the neutral cysteine protease bleomycin hydrolase. Neuroscience. 146:890–900. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Chaitanya GV, Steven AJ and Babu PP: PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 8:312010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen Y, Xu R, Chen J, Li X and He Q: Cleavage of bleomycin hydrolase by caspase-3 during apoptosis. Oncol Rep 30: 939-944, 2013.
APA
Chen, Y., Xu, R., Chen, J., Li, X., & He, Q. (2013). Cleavage of bleomycin hydrolase by caspase-3 during apoptosis. Oncology Reports, 30, 939-944. https://doi.org/10.3892/or.2013.2484
MLA
Chen, Y., Xu, R., Chen, J., Li, X., He, Q."Cleavage of bleomycin hydrolase by caspase-3 during apoptosis". Oncology Reports 30.2 (2013): 939-944.
Chicago
Chen, Y., Xu, R., Chen, J., Li, X., He, Q."Cleavage of bleomycin hydrolase by caspase-3 during apoptosis". Oncology Reports 30, no. 2 (2013): 939-944. https://doi.org/10.3892/or.2013.2484
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Y, Xu R, Chen J, Li X and He Q: Cleavage of bleomycin hydrolase by caspase-3 during apoptosis. Oncol Rep 30: 939-944, 2013.
APA
Chen, Y., Xu, R., Chen, J., Li, X., & He, Q. (2013). Cleavage of bleomycin hydrolase by caspase-3 during apoptosis. Oncology Reports, 30, 939-944. https://doi.org/10.3892/or.2013.2484
MLA
Chen, Y., Xu, R., Chen, J., Li, X., He, Q."Cleavage of bleomycin hydrolase by caspase-3 during apoptosis". Oncology Reports 30.2 (2013): 939-944.
Chicago
Chen, Y., Xu, R., Chen, J., Li, X., He, Q."Cleavage of bleomycin hydrolase by caspase-3 during apoptosis". Oncology Reports 30, no. 2 (2013): 939-944. https://doi.org/10.3892/or.2013.2484
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team