The Dual Function of KDM5C in Both Gene Transcriptional Activation and Repression Promotes Breast Cancer Cell Growth and Tumorigenesis

Autor: Bing-ling Peng, Jia Yi, Wen-juan Zhang, Shaowei Li, Hai-feng Shen, Ying Huang, Wen-Juan Li, Rui Rong, Michael G. Rosenfeld, Xiao‐yan Chen, Tingting Li, Kenny Ohgi, Yaohui He, Lei Wang, Jun-yi Liu, Guo-sheng Hu, Wen Liu
Rok vydání: 2020
Předmět:
Transcriptional Activation
Jumonji C domain‐containing protein
Carcinogenesis
General Chemical Engineering
Science
General Physics and Astronomy
Medicine (miscellaneous)
Repressor
Breast Neoplasms
02 engineering and technology
Biology
010402 general chemistry
medicine.disease_cause
01 natural sciences
Biochemistry
Genetics and Molecular Biology (miscellaneous)

breast cancer
Cell Line
Tumor

Transcriptional regulation
medicine
Humans
General Materials Science
Epigenetics
Research Articles
Cell Proliferation
Histone Demethylases
Activator (genetics)
Cell growth
estrogen and estrogen receptor
General Engineering
021001 nanoscience & nanotechnology
0104 chemical sciences
Cell biology
Cell Transformation
Neoplastic

biology.protein
Demethylase
type I interferon
Female
0210 nano-technology
Estrogen receptor alpha
Research Article
Zdroj: Advanced Science
Advanced Science, Vol 8, Iss 9, Pp n/a-n/a (2021)
ISSN: 2198-3844
Popis: Emerging evidence suggested that epigenetic regulators can exhibit both activator and repressor activities in gene transcriptional regulation and disease development, such as cancer. However, how these dual activities are regulated and coordinated in specific cellular contexts remains elusive. Here, it is reported that KDM5C, a repressive histone demethylase, unexpectedly activates estrogen receptor alpha (ERα)‐target genes, and meanwhile suppresses type I interferons (IFNs) and IFN‐stimulated genes (ISGs) to promote ERα‐positive breast cancer cell growth and tumorigenesis. KDM5C‐interacting protein, ZMYND8, is found to be involved in both processes. Mechanistically, KDM5C binds to active enhancers and recruits the P‐TEFb complex to activate ERα‐target genes, while inhibits TBK1 phosphorylation in the cytosol to repress type I IFNs and ISGs. Pharmacological inhibition of both ERα and KDM5C is effective in inhibiting cell growth and tumorigenesis. Taken together, it is revealed that the dual activator and repressor nature of an epigenetic regulator together contributes to cancer development.
A histone demethylase named KDM5C activates estrogen/estrogen receptor alpha‐target genes to promote cancer cell growth, while suppresses type I interferons and interferon‐stimulated genes to escape from immune surveillance. The dual activator and repressor nature of KDM5C together contributes to cancer development.
Databáze: OpenAIRE