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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
May 2013 Volume 42 Issue 5

Full Size Image

Cover Legend PDF

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
May 2013 Volume 42 Issue 5

Full Size Image

Cover Legend PDF

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

cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases

  • Authors:
    • Martine Müller Kloster
    • Elin Hallan Naderi
    • Ingvild Haaland
    • Bjørn Tore Gjertsen
    • Heidi Kiil Blomhoff
    • Soheil Naderi
  • View Affiliations / Copyright

    Affiliations: Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway, Institute of Medicine, Hematology Section, Haukeland University Hospital, University of Bergen, N-5021 Bergen, Norway
  • Pages: 1815-1821
    |
    Published online on: March 8, 2013
       https://doi.org/10.3892/ijo.2013.1853
  • 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

Activation of cAMP signalling potently inhibits DNA damage-induced apoptosis in acute lymphoblastic leukemia cells by promoting the turnover of p53 protein. Recently, we showed that the cAMP-induced destabilization of p53 in DNA-damaged cells occurs as a result of enhanced interaction between p53 and HDM2. In this report, we present results showing that increased levels of cAMP in cells with DNA damage enhances the deacetylation of p53, an event that facilitates the interaction of p53 with HDM2, thus annulling the stabilizing effect of DNA damage on p53. The combined inhibition of the HDAC and SIRT1 deacetylases abolished the cAMP-mediated deacetylation of p53, implying that cAMP-mediated deacetylation of p53 is dependent on the activity of these two classes of histone deacetylases. Importantly, diminishing the activity of HDACs and SIRT1 was also found to reverse the inhibitory effect of cAMP on the DNA damage-induced p53 stabilization and apoptosis, suggesting the involvement of the p53 acetylation pathway in the anti-apoptotic effect of cAMP signalling.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1. 

Dai C and Gu W: p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med. 16:528–536. 2010. View Article : Google Scholar : PubMed/NCBI

2. 

Appella E and Anderson CW: Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem. 268:2764–2772. 2001. View Article : Google Scholar : PubMed/NCBI

3. 

Brooks CL and Gu W: Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Curr Opin Cell Biol. 15:164–171. 2003. View Article : Google Scholar : PubMed/NCBI

4. 

Brooks CL and Gu W: The impact of acetylation and deacetylation on the p53 pathway. Protein Cell. 2:456–462. 2011. View Article : Google Scholar : PubMed/NCBI

5. 

Gu W and Roeder RG: Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 90:595–606. 1997. View Article : Google Scholar : PubMed/NCBI

6. 

Li M, Luo J, Brooks CL and Gu W: Acetylation of p53 inhibits its ubiquitination by Mdm2. J Biol Chem. 277:50607–50611. 2002. View Article : Google Scholar : PubMed/NCBI

7. 

Liu L, Scolnick DM, Trievel RC, Zhang HB, Marmorstein R, Halazonetis TD and Berger SL: p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol. 19:1202–1209. 1999.PubMed/NCBI

8. 

Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW and Appella E: DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev. 12:2831–2841. 1998. View Article : Google Scholar : PubMed/NCBI

9. 

Wang YH, Tsay YG, Tan BC, Lo WY and Lee SC: Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305. J Biol Chem. 278:25568–25576. 2003. View Article : Google Scholar : PubMed/NCBI

10. 

Tang Y, Zhao W, Chen Y, Zhao Y and Gu W: Acetylation is indispensable for p53 activation. Cell. 133:612–626. 2008. View Article : Google Scholar : PubMed/NCBI

11. 

Torgersen KM, Vang T, Abrahamsen H, Yaqub S and Tasken K: Molecular mechanisms for protein kinase A-mediated modulation of immune function. Cell Signal. 14:1–9. 2002. View Article : Google Scholar : PubMed/NCBI

12. 

Blomhoff HK, Blomhoff R, Stokke T, deLange DC, Brevik K, Smeland EB, Funderud S and Godal T: cAMP-mediated growth inhibition of a B-lymphoid precursor cell line Reh is associated with an early transient delay in G2/M, followed by an accumulation of cells in G1. J Cell Physiol. 137:583–587. 1988. View Article : Google Scholar : PubMed/NCBI

13. 

Blomhoff HK, Smeland EB, Beiske K, Blomhoff R, Ruud E, Bjoro T, Pfeifer-Ohlsson S, Watt R, Funderud S and Godal T: Cyclic AMP-mediated suppression of normal and neoplastic B cell proliferation is associated with regulation of myc and Ha-ras protooncogenes. J Cell Physiol. 131:426–433. 1987. View Article : Google Scholar : PubMed/NCBI

14. 

Naderi S, Gutzkow KB, Christoffersen J, Smeland EB and Blomhoff HK: cAMP-mediated growth inhibition of lymphoid cells in G1: rapid down-regulation of cyclin D3 at the level of translation. Eur J Immunol. 30:1757–1768. 2000. View Article : Google Scholar : PubMed/NCBI

15. 

Naderi S, Wang JY, Chen TT, Gutzkow KB and Blomhoff HK: cAMP-mediated inhibition of DNA replication and S phase progression: involvement of Rb, p21Cip1, and PCNA. Mol Biol Cell. 16:1527–1542. 2005. View Article : Google Scholar : PubMed/NCBI

16. 

Naderi EH, Findley HW, Ruud E, Blomhoff HK and Naderi S: Activation of cAMP signaling inhibits DNA damage-induced apoptosis in BCP-ALL cells through abrogation of p53 accumulation. Blood. 114:608–618. 2009. View Article : Google Scholar : PubMed/NCBI

17. 

Naderi EH, Jochemsen AG, Blomhoff HK and Naderi S: Activation of cAMP signaling interferes with stress-induced p53 accumulation in ALL-derived cells by promoting the interaction between p53 and HDM2. Neoplasia. 13:653–663. 2011.PubMed/NCBI

18. 

Rosenfeld C, Goutner A, Choquet C, Venuat AM, Kayibanda B, Pico JL and Greaves MF: Phenotypic characterisation of a unique non-T, non-B acute lymphoblastic leukaemia cell line. Nature. 267:841–843. 1977. View Article : Google Scholar : PubMed/NCBI

19. 

Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI

20. 

Cai R, Kwon P, Yan-Neale Y, Sambuccetti L, Fischer D and Cohen D: Mammalian histone deacetylase 1 protein is post-translationally modified by phosphorylation. Biochem Biophys Res Commun. 283:445–453. 2001. View Article : Google Scholar : PubMed/NCBI

21. 

Du M, Perry RL, Nowacki NB, Gordon JW, Salma J, Zhao J, Aziz A, Chan J, Siu KW and McDermott JC: Protein kinase A represses skeletal myogenesis by targeting myocyte enhancer factor 2D. Mol Cell Biol. 28:2952–2970. 2008. View Article : Google Scholar : PubMed/NCBI

22. 

Gerhart-Hines Z, Dominy JE Jr, Blattler SM, Jedrychowski MP, Banks AS, Lim JH, Chim H, Gygi SP and Puigserver P: The cAMP/PKA pathway rapidly activates SIRT1 to promote fatty acid oxidation independently of changes in NAD(+). Mol Cell. 44:851–863. 2011.PubMed/NCBI

23. 

Ha CH, Kim JY, Zhao J, Wang W, Jhun BS, Wong C and Jin ZG: PKA phosphorylates histone deacetylase 5 and prevents its nuclear export, leading to the inhibition of gene transcription and cardiomyocyte hypertrophy. Proc Natl Acad Sci USA. 107:15467–15472. 2010. View Article : Google Scholar : PubMed/NCBI

24. 

Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L and Gu W: Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 107:137–148. 2001. View Article : Google Scholar : PubMed/NCBI

25. 

Wang X, Taplick J, Geva N and Oren M: Inhibition of p53 degradation by Mdm2 acetylation. FEBS Lett. 561:195–201. 2004. View Article : Google Scholar : PubMed/NCBI

26. 

Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J and Gu W: Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 416:648–653. 2002. View Article : Google Scholar : PubMed/NCBI

27. 

Batty N, Malouf GG and Issa JP: Histone deacetylase inhibitors as anti-neoplastic agents. Cancer Lett. 280:192–200. 2009. View Article : Google Scholar : PubMed/NCBI

28. 

Khan O and La Thangue NB: HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol Cell Biol. 90:85–94. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kloster MM, Naderi EH, Haaland I, Gjertsen BT, Blomhoff HK and Naderi S: cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases. Int J Oncol 42: 1815-1821, 2013.
APA
Kloster, M.M., Naderi, E.H., Haaland, I., Gjertsen, B.T., Blomhoff, H.K., & Naderi, S. (2013). cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases. International Journal of Oncology, 42, 1815-1821. https://doi.org/10.3892/ijo.2013.1853
MLA
Kloster, M. M., Naderi, E. H., Haaland, I., Gjertsen, B. T., Blomhoff, H. K., Naderi, S."cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases". International Journal of Oncology 42.5 (2013): 1815-1821.
Chicago
Kloster, M. M., Naderi, E. H., Haaland, I., Gjertsen, B. T., Blomhoff, H. K., Naderi, S."cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases". International Journal of Oncology 42, no. 5 (2013): 1815-1821. https://doi.org/10.3892/ijo.2013.1853
Copy and paste a formatted citation
x
Spandidos Publications style
Kloster MM, Naderi EH, Haaland I, Gjertsen BT, Blomhoff HK and Naderi S: cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases. Int J Oncol 42: 1815-1821, 2013.
APA
Kloster, M.M., Naderi, E.H., Haaland, I., Gjertsen, B.T., Blomhoff, H.K., & Naderi, S. (2013). cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases. International Journal of Oncology, 42, 1815-1821. https://doi.org/10.3892/ijo.2013.1853
MLA
Kloster, M. M., Naderi, E. H., Haaland, I., Gjertsen, B. T., Blomhoff, H. K., Naderi, S."cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases". International Journal of Oncology 42.5 (2013): 1815-1821.
Chicago
Kloster, M. M., Naderi, E. H., Haaland, I., Gjertsen, B. T., Blomhoff, H. K., Naderi, S."cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases". International Journal of Oncology 42, no. 5 (2013): 1815-1821. https://doi.org/10.3892/ijo.2013.1853
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