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

Jialiang Li1, Ke Shi1, Tianqi Xu1

  • 1Key Laboratory of Saline‑Alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin, Heilongjiang 150040, P.R. China.

International Journal of Oncology
|December 28, 2020
PubMed
Summary

The cyclin D binding myb-like transcription factor 1 (DMTF1) gene has three isoforms. DMTF1β and γ isoforms promote breast cancer by antagonizing the tumor-suppressive DMTF1α, impacting patient prognosis.

Keywords:
cyclin D binding myb-like transcription factor 1alternative splicingisoformsgene expressionbreast cancer

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Area of Science:

  • Molecular Biology
  • Cancer Genetics

Background:

  • The DMTF1 gene, a tumor suppressor, produces three mRNA isoforms: DMTF1α, β, and γ.
  • DMTF1α exhibits tumor-suppressive functions, while DMTF1β shows oncogenic activity; DMTF1γ's role is unclear.

Purpose of the Study:

  • Investigate mechanisms regulating DMTF1 isoform expression.
  • Characterize the functional interactions between DMTF1β, γ, and DMTF1α.

Main Methods:

  • Analysis of mRNA stability and protein expression.
  • Nuclear localization studies using specific residue identification (K52, R53).
  • Assays to determine protein-protein interactions and promoter activity modulation.

Main Results:

  • Specific transcript regions in DMTF1β and γ reduce their mRNA stability and protein levels.
  • DMTF1β and γ proteins are less stable than DMTF1α.
  • All isoforms localize to the nucleus, dependent on residues K52 and R53.
  • DMTF1β and γ associate with DMTF1α, inhibiting its ARF promoter transactivation.

Conclusions:

  • DMTF1β and γ isoforms possess oncogenic roles in breast cancer.
  • Elevated DMTF1β/α and γ/α ratios correlate with poor breast cancer prognosis.
  • Understanding these isoform interactions is crucial for breast cancer research.