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 |
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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 |
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