Deptor, the DEP-domain containing mTOR-interacting protein, is a key regulator of the mechanistic target of rapamycin (mTOR) [1,2,3,5]. It belongs to the mTORC1 and mTORC2 complexes and can inhibit mTOR kinase activity [2,3]. As a natural mTOR inhibitor, Deptor is involved in multiple molecular pathways such as cell growth, apoptosis, autophagy, ER stress response, and has been associated with transcriptional regulation [2]. The mTOR pathway, regulated by Deptor, is crucial for diverse cellular processes in response to environmental stimuli, making Deptor important for maintaining cellular homeostasis [2,3].

In lung cancer, Deptor deletion fully rescued the tumor inhibitory effect of Ube2c deletion in the KrasG12D lung tumor model, indicating its role in regulating cell cycle progression and autophagy in this context [4]. In another study, Deptor deletion accelerated KrasG12D;p53fl/fl-induced lung tumorigenesis and shortened mouse lifespan via the activation of EGFR-mTOR signals, suggesting it acts as a tumor suppressor in lung tumorigenesis [6]. In osteoporosis, Deptor ablation in bone marrow-derived mesenchymal stem cells (BMSCs) alleviated bone loss and reduced marrow fat accumulation in mice, as Deptor was found to exacerbate bone-fat imbalance by modulating BMSC differentiation [7].

In conclusion, Deptor is an important regulator of the mTOR pathway, influencing multiple cellular processes. Gene-knockout mouse models have been instrumental in revealing its role in diseases such as lung cancer and osteoporosis. These studies provide valuable insights into the biological functions of Deptor and suggest its potential as a therapeutic target in these disease areas.

References:

1. Perez-Tejeiro, Jose Miguel, Csukasi, Fabiana. 2021. DEPTOR in Skeletal Development and Diseases. In Frontiers in genetics, 12, 667283. doi:10.3389/fgene.2021.667283. https://pubmed.ncbi.nlm.nih.gov/34122519/

2. Catena, Valeria, Fanciulli, Maurizio. 2017. Deptor: not only a mTOR inhibitor. In Journal of experimental & clinical cancer research : CR, 36, 12. doi:10.1186/s13046-016-0484-y. https://pubmed.ncbi.nlm.nih.gov/28086984/

3. Morales-Martinez, Mario, Lichtenstein, Alan, Vega, Mario I. 2021. Function of Deptor and its roles in hematological malignancies. In Aging, 13, 1528-1564. doi:10.18632/aging.202462. https://pubmed.ncbi.nlm.nih.gov/33412518/

4. Zhang, Shizhen, You, Xiahong, Zheng, Yawen, Xiong, Xiufang, Sun, Yi. 2023. The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells. In The Journal of clinical investigation, 133, . doi:10.1172/JCI162434. https://pubmed.ncbi.nlm.nih.gov/36548081/

5. Caron, Alexandre, Briscoe, David M, Richard, Denis, Laplante, Mathieu. . DEPTOR at the Nexus of Cancer, Metabolism, and Immunity. In Physiological reviews, 98, 1765-1803. doi:10.1152/physrev.00064.2017. https://pubmed.ncbi.nlm.nih.gov/29897294/

6. Gong, Longyuan, Shu, Jianfeng, Chen, Xiaoyu, Xiong, Xiufang, Zhao, Yongchao. 2021. DEPTOR inhibits lung tumorigenesis by inactivating the EGFR-mTOR signals. In Cancer letters, 519, 263-276. doi:10.1016/j.canlet.2021.07.031. https://pubmed.ncbi.nlm.nih.gov/34320372/

7. Ouyang, Zhicong, Kang, Dawei, Li, Kai, Huang, Bin, Li, Qingchu. 2022. DEPTOR exacerbates bone-fat imbalance in osteoporosis by transcriptionally modulating BMSC differentiation. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 151, 113164. doi:10.1016/j.biopha.2022.113164. https://pubmed.ncbi.nlm.nih.gov/35609371/