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

Li,Jialiang; Shi,Ke; Xu,Tianqi; Hu,Jingru; Li,Tianxin; Li,Guangyue; Chen,Kuida; Li,Dangdang; Inoue,Kazushi; Sui,Guangchao

doi:10.3892/ijo.2020.5146

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
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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
Published online on: November 10, 2020 https://doi.org/10.3892/ijo.2020.5146
Pages: 20-32
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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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.

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