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SOX9 is controlled by the BRD4 inhibitor JQ1 via multiple regulation mechanisms
- Source :
- Biochemical and Biophysical Research Communications. 511:746-752
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- SOX9 is a key transcription factor during cell differentiation, sex determination, and tumorigenesis. However, the detailed mechanisms of its targeting strategy remain elusive. To investigate possibilities of targeting SOX9 with epigenetic drugs and the precise underlying mechanisms, two human cancer cell lines were chosen as model systems, which showed high SOX9 expression and anti-tumorigenic effects upon loss of SOX9. Histone acetylation-related screening of a small panel of epigenetic drugs revealed that the bromodomain reader inhibitor JQ1 dramatically downregulated SOX9 through multiple regulation steps, namely, transcription, BRD4-SOX9 protein-protein interaction, and further protein stability. These findings suggest that BRD4 inhibition is a novel therapeutic strategy for diseases characterized by SOX9 overexpression.
- Subjects :
- 0301 basic medicine
endocrine system
BRD4
animal structures
Cellular differentiation
Biophysics
Down-Regulation
Cell Cycle Proteins
medicine.disease_cause
Biochemistry
Epigenesis, Genetic
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Transcription (biology)
Cell Line, Tumor
Neoplasms
medicine
Humans
Epigenetics
Molecular Biology
Transcription factor
biology
SOX9 Transcription Factor
Azepines
Cell Biology
Triazoles
musculoskeletal system
Cell biology
Bromodomain
Gene Expression Regulation, Neoplastic
030104 developmental biology
Histone
030220 oncology & carcinogenesis
embryonic structures
biology.protein
Carcinogenesis
Transcription Factors
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 511
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....b9fb54b1ad898736f63c6eec5485ccb5