Jmjd7, or Jumonji-C (JmjC) domain-containing 7, is a 2-oxoglutarate (2OG)-dependent oxygenase [1]. It has been shown to play significant roles in multiple biological processes and diseases. Functionally, it catalyzes (3S)-lysyl hydroxylation of developmentally regulated GTP-binding proteins 1 and 2 (DRG1/2), which are members of the translation factor (TRAFAC) family of GTPases [2]. It also has been reported to have histone endopeptidase activity, preferentially cleaving the tails of histones containing methylated arginines [4]. It may be involved in pathways related to transcription regulation, as its protease activities could potentially define a mechanism for removing histone tails with methylated arginine residues, thereby influencing transcription [4].

Knockdown of Jmjd7 in RAW 264.7 cells and murine bone marrow macrophages (BMMs) enhanced osteoclast differentiation and increased the expression of osteoclast-related genes, suggesting that Jmjd7 negatively regulates osteoclastogenesis and may be a therapeutic target for bone-related diseases [3]. Ablation of the read-through fusion gene JMJD7-PLA2G4B significantly inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cells, indicating that JMJD7-PLA2G4B may serve as an important therapeutic target and prognostic marker for HNSCC development and progression [5].

In conclusion, Jmjd7 has diverse functions, including lysyl hydroxylation and histone endopeptidase activities. Its role in negatively regulating osteoclast differentiation and the oncogenic function of its fusion gene JMJD7-PLA2G4B in HNSCC highlight its importance in bone-related diseases and cancer. Studies on Jmjd7 using knockdown models provide insights into its biological functions and potential as a therapeutic target in these disease areas.

References:

1. Zhang, Wenqing, Li, Kan, Wang, Tianqi, Wu, Ming, Li, Linli. 2021. Discovery of JMJD7 inhibitors with the aid of virtual screening and bioactivity evaluation. In Bioorganic & medicinal chemistry letters, 45, 128139. doi:10.1016/j.bmcl.2021.128139. https://pubmed.ncbi.nlm.nih.gov/34048880/

2. Markolovic, Suzana, Zhuang, Qinqin, Wilkins, Sarah E, Coleman, Mathew L, Schofield, Christopher J. 2018. The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases. In Nature chemical biology, 14, 688-695. doi:10.1038/s41589-018-0071-y. https://pubmed.ncbi.nlm.nih.gov/29915238/

3. Liu, Yingci, Arai, Atsushi, Kim, Terresa, Park, No-Hee, Kim, Reuben H. . Histone Demethylase Jmjd7 Negatively Regulates Differentiation of Osteoclast. In The Chinese journal of dental research, 21, 113-118. doi:10.3290/j.cjdr.a40437. https://pubmed.ncbi.nlm.nih.gov/29808174/

4. Liu, Haolin, Wang, Chao, Lee, Schuyler, Hagman, James, Zhang, Gongyi. 2017. Clipping of arginine-methylated histone tails by JMJD5 and JMJD7. In Proceedings of the National Academy of Sciences of the United States of America, 114, E7717-E7726. doi:10.1073/pnas.1706831114. https://pubmed.ncbi.nlm.nih.gov/28847961/

5. Cheng, Yingduan, Wang, Yi, Li, Jiong, Chang, Insoon, Wang, Cun-Yu. . A novel read-through transcript JMJD7-PLA2G4B regulates head and neck squamous cell carcinoma cell proliferation and survival. In Oncotarget, 8, 1972-1982. doi:10.18632/oncotarget.14081. https://pubmed.ncbi.nlm.nih.gov/28030848/