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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October-2015 Volume 10 Issue 4

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
October-2015 Volume 10 Issue 4

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

Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells

  • Authors:
    • Wen‑Long Ma
    • Lin Wang
    • Ling‑Xia Liu
    • Xiu‑Li Wang
  • View Affiliations / Copyright

    Affiliations: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, P.R. China, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, P.R. China
  • Pages: 2277-2282
    |
    Published online on: August 17, 2015
       https://doi.org/10.3892/ol.2015.3617
  • 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

The p16INK4a protein (p16) has been reported to be a tumor suppressor gene that suppresses the proliferation of cells through the direct inhibition of cell cycle progression. Accordingly, p16 is a potential target for cancer gene therapy. In the present study, the arginine 22, 131 and 138 residues of p16 were found to be methylation sites, as the mutation of these arginine residues to lysine resulted in the hypomethylation of p16. Furthermore, the protein arginine methyltransferases (PRMTs), such as PRMT1, PRMT4 and PRMT6, were determined to be involved in the methylation of the p16 arginine residues. PRMT6 effectively reduced the intensity of the association between p16 and CDK4, and also weakened the function of p16 in preventing cell proliferation. In addition, the p16 protein was found to be phosphorylated in various cell lines, and mutations in the serine residues weakened the cell cycle arrest and induction of apoptosis mediated by p16. Preliminarily, the crosstalk between the phosphorylation and arginine methylation modification of p16 was examined. These findings predict a role for serine phosphorylation against arginine methylation of p16.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G and Hara E: Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. Nature. 409:1067–1070. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Gizard F, Amant C, Barbier O, Bellosta S, Robillard R, Percevault F, Sevestre H, Krimpenfort P, Corsini A, Rochette J, et al: PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a. J Clin Invest. 115:3228–3238. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Wang X, Feng Y, Xu L, Chen Y, Zhang Y, Su D, Ren G, Lu J and Huang B: YY1 restrained cell senescence through repressing the transcription of p16. Biochim Biophys Acta. 1783:1876–1883. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Wang X, Pan L, Feng Y, Wang Y, Han Q, Han L, Han S, Guo J, Huang B and Lu J: P300 plays a role in p16 (INK4a) expression and cell cycle arrest. Oncogene. 27:1894–1904. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Feng Y, Wang X, Xu L, Pan H, Zhu S, Liang Q, Huang B and Lu J: The transcription factor ZBP-89 suppresses p16 expression through a histone modification mechanism to affect cell senescence. FEBS J. 276:4197–4206. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Gump J, Stokoe D and McCormick F: Phosphorylation of p16INK4A correlates with Cdk4 association. J Biol Chem. 278:6619–6622. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Wang X, Huang Y, Zhao J, Zhang Y, Lu J and Huang B: Suppression of PRMT6-mediated arginine methylation of p16 protein potentiates its ability to arrest A549 cell proliferation. Int J Biochem Cell Biol. 44:2333–2341. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Pahlich S, Zakaryan RP and Gehring H: Protein arginine methylation: Cellular functions and methods of analysis. Biochim Biophys Acta. 1764:1890–1903. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Di Lorenzo A and Bedford MT: Histone arginine methylation. FEBS Lett. 585:2024–2031. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Han L, Lu J, Pan L, Wang X, Shao Y, Han S and Huang B: Histone acetyltransferase p300 regulates the transcription of human erythroid-specific 5-aminolevulinate synthase gene. Biochem Biophys Res Commun. 348:799–806. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Xie B, Invernizzi CF, Richard S and Wainberg MA: Arginine methylation of the human immunodeficiency virus type 1 Tat protein by PRMT6 negatively affects Tat Interactions with both cyclin T1 and the Tat transactivation region. J Virol. 81:4226–4234. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Frankel A, Yadav N, Lee J, Branscombe TL, Clarke S and Bedford MT: The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. J Biol Chem. 277:3537–3543. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Boulanger MC, Liang C, Russell RS, Lin R, Bedford MT, Wainberg MA and Richard S: Methylation of Tat by PRMT6 regulates human immunodeficiency virus type 1 gene expression. J Virol. 79:124–131. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Strahl BD and Allis CD: The language of covalent histone modifications. Nature. 403:41–45. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Berger SL: The complex language of chromatin regulation during transcription. Nature. 447:407–412. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Sandhu C, Peehl DM and Slingerland J: p16INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells. Cancer Res. 60:2616–2622. 2000.PubMed/NCBI

18 

Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y and Fukamizu A: Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol Cell. 32:221–231. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Hsu JM, Chen CT, Chou CK, Kuo HP, Li LY, Lin CY, Lee HJ, Wang YN, Liu M, Liao HW, et al: Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol. 13:174–181. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma WL, Wang L, Liu LX and Wang XL: Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells. Oncol Lett 10: 2277-2282, 2015.
APA
Ma, W., Wang, L., Liu, L., & Wang, X. (2015). Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells. Oncology Letters, 10, 2277-2282. https://doi.org/10.3892/ol.2015.3617
MLA
Ma, W., Wang, L., Liu, L., Wang, X."Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells". Oncology Letters 10.4 (2015): 2277-2282.
Chicago
Ma, W., Wang, L., Liu, L., Wang, X."Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells". Oncology Letters 10, no. 4 (2015): 2277-2282. https://doi.org/10.3892/ol.2015.3617
Copy and paste a formatted citation
x
Spandidos Publications style
Ma WL, Wang L, Liu LX and Wang XL: Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells. Oncol Lett 10: 2277-2282, 2015.
APA
Ma, W., Wang, L., Liu, L., & Wang, X. (2015). Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells. Oncology Letters, 10, 2277-2282. https://doi.org/10.3892/ol.2015.3617
MLA
Ma, W., Wang, L., Liu, L., Wang, X."Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells". Oncology Letters 10.4 (2015): 2277-2282.
Chicago
Ma, W., Wang, L., Liu, L., Wang, X."Effect of phosphorylation and methylation on the function of the p16INK4a protein in non-small cell lung cancer A549 cells". Oncology Letters 10, no. 4 (2015): 2277-2282. https://doi.org/10.3892/ol.2015.3617
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