Mechanisms regulating DMTF1ß/γ expression and their functional interplay with DMTF1α.
Int J Oncol
; 58(1): 20-32, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-33367929
ABSTRACT
The cyclin D binding myblike transcription factor 1 (DMTF1), a haploinsufficient tumor suppressor gene, has 3 alternatively spliced mRNA isoforms encoding DMTF1α, ß and γ proteins. Previous studies have indicated a tumor suppressive role of DMTF1α and the oncogenic activity of DMTF1ß, 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 DMTF1ß and γ with DMTF1α was characterized. It was found that specific regions of DMTF1ß and γ transcripts can impair their mRNA integrity or stability, and thus reduce protein expression levels. Additionally, DMTF1ß 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 DMTF1ß and γ could associate with DMTF1α and antagonize its transactivation of the ARF promoter. Consistently, the ratios of both DMTF1ß/α and γ/α were significantly associated with a poor prognoses of breast cancer patients, suggesting oncogenic roles of DMTF1ß and γ isoforms in breast cancer development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Neoplasias de la Mama
/
Regulación Neoplásica de la Expresión Génica
/
Carcinogénesis
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article