Abstract
It was more than a decade ago that PHF8, KDM7A/JHDM1D and PHF2 were first proposed to be a histone demethylase family and were named as KDM7 (lysine demethylase) family. Since then, knowledge of their demethylation activities, roles as co-regulators of transcription and roles in development and diseases such as cancer has been steadily growing. The demethylation activities of PHF8 and KDM7A toward various methylated histones including H3K9me2/1, H3K27me2 and H4K20me1 have been identified and proven in various cell types. In contrast, PHF2, due to a mutation of a key residue in an iron-binding domain, demethylates H3K9me2 upon PKA-mediated phosphorylation. Interestingly, it was reported that PHF2 possesses an unusual H4K20me3 demethylation activity, which was not observed for PHF8 and KDM7A. PHF8 has been most extensively studied with respect to its roles in development and oncogenesis, revealing that it contributes to regulation of the cell cycle, cell viability and cell migration. Moreover, accumulating lines of evidence demonstrated that the KDM7 family members are subjected to post-transcriptional and post-translational regulations, leading to a higher horizon for evaluating their actual protein expression and functions in development and cancer. This chapter provides a general view of the current understanding of the regulation and functions of the KDM7 family and discusses their potential as therapeutic targets in cancer as well as perspectives for further studies.
Present address: Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
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Shao, P., Liu, Q., Qi, H.H. (2023). KDM7 Demethylases: Regulation, Function and Therapeutic Targeting. In: Yan, Q. (eds) Targeting Lysine Demethylases in Cancer and Other Human Diseases. Advances in Experimental Medicine and Biology, vol 1433. Springer, Cham. https://doi.org/10.1007/978-3-031-38176-8_8
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