Dek-KO Mouse

DEK, an oncogene, is a highly conserved nuclear factor [2,4]. It plays important roles in regulating multiple cellular processes, such as epigenetic and transcriptional regulation [4]. DEK is also involved in cellular transformation, affecting processes like self-renewal, proliferation, and apoptosis [4]. The secreted form of DEK can regulate hematopoiesis by activating signaling through the CXCL2 receptor, which impacts the proliferation of hematopoietic stem cells and the number of hematopoietic progenitor cells [3].

In hematopoietic stem cells (HSCs), nuclear DEK is crucial. HSCs lacking DEK show defects in long-term self-renew capacity, leading to impaired hematopoiesis [1]. DEK deficiency reduces quiescence and accelerates mitochondrial metabolism in HSCs, in part by activating mTOR signaling [1]. At the molecular level, DEK recruits the corepressor NCoR1 to repress histone 3 acetylation at lysine 27 (H3K27ac), restricting chromatin accessibility and governing the expression of quiescence-associated genes [1].

In conclusion, DEK is essential for maintaining normal cellular functions, especially in hematopoiesis. The study of DEK-deficient mouse models has revealed its key role in preserving HSC potential, uncovering a link between chromatin remodelers and HSC homeostasis, which has important implications for understanding and potentially treating hematopoietic-related diseases [1].

References:

1. Chen, Zhe, Huo, Dawei, Li, Lei, Chen, Jieping, Hou, Yu. . Nuclear DEK preserves hematopoietic stem cells potential via NCoR1/HDAC3-Akt1/2-mTOR axis. In The Journal of experimental medicine, 218, . doi:10.1084/jem.20201974. https://pubmed.ncbi.nlm.nih.gov/33755722/

2. Ishida, Kazuhisa, Nakashima, Takayuki, Shibata, Toshiyuki, Hara, Akira, Tomita, Hiroyuki. 2020. Role of the DEK oncogene in the development of squamous cell carcinoma. In International journal of clinical oncology, 25, 1563-1569. doi:10.1007/s10147-020-01735-5. https://pubmed.ncbi.nlm.nih.gov/32656741/

3. Bodine, David M. 2019. All hands on DEK. In The Journal of clinical investigation, 129, 2205-2206. doi:10.1172/JCI128986. https://pubmed.ncbi.nlm.nih.gov/31107244/

4. Sandén, C, Gullberg, U. 2015. The DEK oncoprotein and its emerging roles in gene regulation. In Leukemia, 29, 1632-6. doi:10.1038/leu.2015.72. https://pubmed.ncbi.nlm.nih.gov/25765544/