DET1, short for DE-ETIOLATED 1, is an evolutionarily conserved component of the ubiquitination machinery. It is a key repressor in Arabidopsis photomorphogenesis, working with CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) to form CRL4-based E3 ubiquitin ligases. These ligases mediate the degradation of photomorphogenic transcription factors like ELONGATED HYPOCOTYL 5 (HY5), thus controlling multiple gene-regulatory networks. DET1 is also involved in other processes such as thermomorphogenesis, histone H2B monoubiquitination regulation, and seed germination [1,2,3,4,6].

In mice, deletion of Det1 in neural stem cells leads to hydrocephalus, cerebellar dysplasia, and neonatal lethality, while complete lack of Det1 results in embryonic death. In humans, a homozygous DET1R26W mutation impairs binding to DDB1, compromising E3 ligase function. This mutation is linked to lethal developmental abnormalities, as human-induced pluripotent stem cells with this mutation show defective mitochondrial homeostasis and aberrant caspase-dependent cell death when differentiated into neurons [5].

In conclusion, DET1 plays crucial roles in plant development processes such as photomorphogenesis, thermomorphogenesis, and seed germination. In mammals, especially in mice and humans, DET1 is essential for normal neurological development. The study of DET1 through gene-knockout models in mice has revealed its significance in preventing neurological defects and lethal developmental abnormalities.

References:

1. Cañibano, Esther, Bourbousse, Clara, García-León, Marta, Rubio, Vicente, Fonseca, Sandra. 2021. DET1-mediated COP1 regulation avoids HY5 activity over second-site gene targets to tune plant photomorphogenesis. In Molecular plant, 14, 963-982. doi:10.1016/j.molp.2021.03.009. https://pubmed.ncbi.nlm.nih.gov/33711490/

2. Lau, On Sun, Deng, Xing Wang. 2012. The photomorphogenic repressors COP1 and DET1: 20 years later. In Trends in plant science, 17, 584-93. doi:10.1016/j.tplants.2012.05.004. https://pubmed.ncbi.nlm.nih.gov/22705257/

3. Yuan, Shuai, Li, Yan, Li, Yayi, Yang, Feng, Yao, Xiuhong. 2024. DET1 modulates ATAF1-repressed thermosensory elongation through ubiquitination in Arabidopsis. In Plant cell reports, 44, 7. doi:10.1007/s00299-024-03402-9. https://pubmed.ncbi.nlm.nih.gov/39688715/

4. Nassrallah, Amr, Rougée, Martin, Bourbousse, Clara, Rubio, Vicente, Barneche, Fredy. 2018. DET1-mediated degradation of a SAGA-like deubiquitination module controls H2Bub homeostasis. In eLife, 7, . doi:10.7554/eLife.37892. https://pubmed.ncbi.nlm.nih.gov/30192741/

5. Karayel, Ozge, Soung, Allison, Gurung, Hem, Newton, Kim, Dixit, Vishva M. 2025. Impairment of DET1 causes neurological defects and lethality in mice and humans. In Proceedings of the National Academy of Sciences of the United States of America, 122, e2422631122. doi:10.1073/pnas.2422631122. https://pubmed.ncbi.nlm.nih.gov/39937864/

6. Shi, Hui, Wang, Xin, Mo, Xiaorong, Zhong, Shangwei, Deng, Xing Wang. 2015. Arabidopsis DET1 degrades HFR1 but stabilizes PIF1 to precisely regulate seed germination. In Proceedings of the National Academy of Sciences of the United States of America, 112, 3817-22. doi:10.1073/pnas.1502405112. https://pubmed.ncbi.nlm.nih.gov/25775589/