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
January-2021 Volume 58 Issue 1

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
January-2021 Volume 58 Issue 1

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α

  • Authors:
    • Jialiang Li
    • Ke Shi
    • Tianqi Xu
    • Jingru Hu
    • Tianxin Li
    • Guangyue Li
    • Kuida Chen
    • Dangdang Li
    • Kazushi Inoue
    • Guangchao Sui
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Saline‑Alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin, Heilongjiang 150040, P.R. China, Department of Pathology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston‑Salem, NC 27157, USA
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Pages: 20-32
    |
    Published online on: November 10, 2020
       https://doi.org/10.3892/ijo.2020.5146
  • 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 cyclin D binding myb‑like transcription factor 1 (DMTF1), a haplo‑insufficient tumor suppressor gene, has 3 alternatively spliced mRNA isoforms encoding DMTF1α, β and γ proteins. Previous studies have indicated a tumor suppressive role of DMTF1α and the oncogenic activity of DMTF1β, while the function of DMTF1γ remains largely undetermined. In the present study, the mechanisms regulating DMTF1 isoform expression were investigated and the functional interplay of DMTF1β and γ with DMTF1α was characterized. It was found that specific regions of DMTF1β and γ transcripts can impair their mRNA integrity or stability, and thus reduce protein expression levels. Additionally, DMTF1β and γ proteins exhibited a reduced stability compared to DMTF1α and all 3 DMTF1 isoforms were localized in the nuclei. Two basic residues, K52 and R53, in the DMTF1 isoforms determined their nuclear localization. Importantly, both DMTF1β and γ could associate with DMTF1α and antagonize its transactivation of the ARF promoter. Consistently, the ratios of both DMTF1β/α and γ/α were significantly associated with a poor prognoses of breast cancer patients, suggesting oncogenic roles of DMTF1β and γ isoforms in breast cancer development.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Hirai H and Sherr CJ: Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1. Mol Cell Biol. 16:6457–6467. 1996. View Article : Google Scholar : PubMed/NCBI

2 

Inoue K and Sherr CJ: Gene expression and cell cycle arrest mediated by transcription factor DMP1 is antagonized by D-type cyclins through a cyclin-dependent-kinase-independent mechanism. Mol Cell Biol. 18:1590–1600. 1998. View Article : Google Scholar : PubMed/NCBI

3 

Inoue K, Roussel MF and Sherr CJ: Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1. Proc Natl Acad Sci USA. 96:3993–3998. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Inoue K, Wen R, Rehg JE, Adachi M, Cleveland JL, Roussel MF and Sherr CJ: Disruption of the ARF transcriptional activator DMP1 facilitates cell immortalization, Ras transformation, and tumorigenesis. Genes Dev. 14:1797–1809. 2000.PubMed/NCBI

5 

Inoue K, Zindy F, Randle DH, Rehg JE and Sherr CJ: Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas. Genes Dev. 15:2934–2939. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Fry EA, Taneja P, Maglic D, Zhu S, Sui G and Inoue K: Dmp1α inhibits HER2/neu-induced mammary tumorigenesis. PLoS One. 8:e778702013. View Article : Google Scholar

7 

Zhu S, Mott RT, Fry EA, Taneja P, Kulik G, Sui G and Inoue K: Cooperation between Dmp1 loss and cyclin D1 overexpression in breast cancer. Am J Pathol. 183:1339–1350. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Peng Y, Dong W, Lin TX, Zhong GZ, Liao B, Wang B, Gu P, Huang L, Xie Y, Lu FD, et al: MicroRNA-155 promotes bladder cancer growth by repressing the tumor suppressor DMTF1. Oncotarget. 6:16043–16058. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Yang X, Lou Y, Wang M, Liu C, Liu Y and Huang W: miR-675 promotes colorectal cancer cell growth dependent on tumor suppressor DMTF1. Mol Med Rep. 19:1481–1490. 2019.

10 

Tian N, Li J, Shi J and Sui G: From general aberrant alternative splicing in cancers and its therapeutic application to the discovery of an oncogenic DMTF1 isoform. Int J Mol Sci. 18:1912017. View Article : Google Scholar :

11 

Tschan MP, Fischer KM, Fung VS, Pirnia F, Borner MM, Fey MF, Tobler A and Torbett BE: Alternative splicing of the human cyclin D-binding Myb-like protein (hDMP1) yields a truncated protein isoform that alters macrophage differentiation patterns. J Biol Chem. 278:42750–42760. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Maglic D, Stovall DB, Cline JM, Fry EA, Mallakin A, Taneja P, Caudell DL, Willingham MC, Sui G and Inoue K: DMP1β, a splice isoform of the tumour suppressor DMP1 locus, induces proliferation and progression of breast cancer. J Pathol. 236:90–102. 2015. View Article : Google Scholar :

13 

Tschan MP, Federzoni EA, Haimovici A, Britschgi C, Moser BA, Jin J, Reddy VA, Sheeter DA, Fischer KM, Sun P and Torbett BE: Human DMTF1β antagonizes DMTF1α regulation of the p14(ARF) tumor suppressor and promotes cellular proliferation. Biochim Biophys Acta. 1849:1198–1208. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Niklaus NJ, Humbert M and Tschan MP: Cisplatin sensitivity in breast cancer cells is associated with particular DMTF1 splice variant expression. Biochem Biophys Res Commun. 503:2800–2806. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Mallakin A, Sugiyama T, Kai F, Kai F, Taneja P, Kendig RD, Frazier DP, Maglic D, Matise LA, Willingham MC and Inoue K: The Arf-inducing transcription factor Dmp1 encodes a transcriptional activator of amphiregulin, thrombospondin-1, JunB and Egr1. Int J Cancer. 126:1403–1416. 2010.

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

17 

Wan M, Huang W, Kute TE, Miller LD, Zhang Q, Hatcher H, Wang J, Stovall DB, Russell GB, Cao PD, et al Yang Yin: 1 plays an essential role in breast cancer and negatively regulates p27. Am J Pathol. 180:2120–2133. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Deng Z, Wan M, Cao P, Rao A, Cramer SD and Sui G: Yin Yang 1 regulates the transcriptional activity of androgen receptor. Oncogene. 28:3746–3757. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Kosugi S, Hasebe M, Tomita M and Yanagawa H: Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci USA. 106:10171–10176. 2009. View Article : Google Scholar : PubMed/NCBI

20 

la Cour T, Kiemer L, Mølgaard A, Gupta R, Skriver K and Brunak S: Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel. 17:527–536. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Ryan M, Wong WC, Brown R, Akbani R, Su X, Broom B, Melott J and Weinstein J: TCGASpliceSeq a compendium of alternative mRNA splicing in cancer. Nucleic Acids Res. 44(D1): D1018–D1022. 2016. View Article : Google Scholar :

22 

Martinez RLMC and Naranjo JD: A pretest for choosing between logrank and Wilcoxon tests in the two-sample problem. METRON. 68:111–125. 2010. View Article : Google Scholar

23 

Baker KE and Parker R: Nonsense-mediated mRNA decay: Terminating erroneous gene expression. Curr Opin Cell Biol. 16:293–299. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Chang YF, Imam JS and Wilkinson MF: The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem. 76:51–74. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Latchman DS: Inhibitory transcription factors. Int J Biochem Cell Biol. 28:965–974. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Soutourina J: Transcription regulation by the Mediator complex. Nat Rev Mol Cell Biol. 19:262–274. 2018. View Article : Google Scholar

27 

Khan MA, Jain VK, Rizwanullah M, Ahmad J and Jain K: PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: A review on drug discovery and future challenges. Drug Discov Today. 24:2181–2191. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Garte SJ: The c-myc oncogene in tumor progression. Crit Rev Oncog. 4:435–449. 1993.PubMed/NCBI

29 

Perrier A, Gligorov J, Lefèvre G and Boissan M: The extracellular domain of Her2 in serum as a biomarker of breast cancer. Lab Invest. 98:696–707. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Dittmer J: The role of the transcription factor Ets1 in carcinoma. Semin Cancer Biol. 35:20–38. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li J, Shi K, Xu T, Hu J, Li T, Li G, Chen K, Li D, Inoue K, Sui G, Sui G, et al: Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α. Int J Oncol 58: 20-32, 2021.
APA
Li, J., Shi, K., Xu, T., Hu, J., Li, T., Li, G. ... Sui, G. (2021). Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α. International Journal of Oncology, 58, 20-32. https://doi.org/10.3892/ijo.2020.5146
MLA
Li, J., Shi, K., Xu, T., Hu, J., Li, T., Li, G., Chen, K., Li, D., Inoue, K., Sui, G."Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α". International Journal of Oncology 58.1 (2021): 20-32.
Chicago
Li, J., Shi, K., Xu, T., Hu, J., Li, T., Li, G., Chen, K., Li, D., Inoue, K., Sui, G."Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α". International Journal of Oncology 58, no. 1 (2021): 20-32. https://doi.org/10.3892/ijo.2020.5146
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Shi K, Xu T, Hu J, Li T, Li G, Chen K, Li D, Inoue K, Sui G, Sui G, et al: Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α. Int J Oncol 58: 20-32, 2021.
APA
Li, J., Shi, K., Xu, T., Hu, J., Li, T., Li, G. ... Sui, G. (2021). Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α. International Journal of Oncology, 58, 20-32. https://doi.org/10.3892/ijo.2020.5146
MLA
Li, J., Shi, K., Xu, T., Hu, J., Li, T., Li, G., Chen, K., Li, D., Inoue, K., Sui, G."Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α". International Journal of Oncology 58.1 (2021): 20-32.
Chicago
Li, J., Shi, K., Xu, T., Hu, J., Li, T., Li, G., Chen, K., Li, D., Inoue, K., Sui, G."Mechanisms regulating DMTF1β/γ expression and their functional interplay with DMTF1α". International Journal of Oncology 58, no. 1 (2021): 20-32. https://doi.org/10.3892/ijo.2020.5146
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