Cytl1, also named Protein C17 or C4orf4, is a gene located on human chromosome 4p15-p16 encoding a 126-amino-acid-residue secretory protein. It plays roles in various biological processes. It may regulate chondrogenesis, cartilage homeostasis and osteoarthritis progression, possibly through modulating Sox9 and insulin-like growth factor 1 expression. It also exhibits chemotactic and pro-angiogenic effects, and is associated with multiple signaling pathways such as ERK (mediated by CCR2) and TGF-β-Smad (potentially independent of CCR2) [1].

Cytl1-/-mice show higher bone mass than wild-type littermates and resist ovariectomy-induced bone resorption. In vitro, CYTL1 overexpression or exogenous treatment inhibits the osteogenesis of human mesenchymal stem cells, while CYTL1 knockdown enhances it. Also, CYTL1-/-mice have inhibited osteoclast activity and osteoclastogenesis of bone marrow-derived macrophages, suggesting CYTL1 negatively regulates MSC osteogenesis and positively regulates osteoclastogenesis to modulate bone mass in mice [3]. In breast cancer, intracellular CYTL1 lacking a 1-22 aa signal peptide can inhibit metabolic reprogramming, cell growth and metastasis by stabilizing NDUFV1 [2].

In conclusion, Cytl1 is involved in chondrogenesis, cartilage homeostasis, bone homeostasis and tumor-related processes. Gene-knockout mouse models, like the Cytl1-/-mice, have been crucial in revealing its functions in bone-related diseases and potentially in tumor-associated conditions, helping us understand its role in biological processes and providing insights for therapeutic strategies in related diseases.

References:

1. Zhu, Sipin, Kuek, Vincent, Bennett, Samuel, Rosen, Vicki, Xu, Jiake. 2019. Protein Cytl1: its role in chondrogenesis, cartilage homeostasis, and disease. In Cellular and molecular life sciences : CMLS, 76, 3515-3523. doi:10.1007/s00018-019-03137-x. https://pubmed.ncbi.nlm.nih.gov/31089746/

2. Xue, Wenwen, Li, Xin, Li, Wuhao, Shen, Yan, Xu, Qiang. 2022. Intracellular CYTL1, a novel tumor suppressor, stabilizes NDUFV1 to inhibit metabolic reprogramming in breast cancer. In Signal transduction and targeted therapy, 7, 35. doi:10.1038/s41392-021-00856-1. https://pubmed.ncbi.nlm.nih.gov/35115484/

3. Shin, Youngnim, Won, Yoonkyung, Yang, Jeong-In, Chun, Jang-Soo. 2019. CYTL1 regulates bone homeostasis in mice by modulating osteogenesis of mesenchymal stem cells and osteoclastogenesis of bone marrow-derived macrophages. In Cell death & disease, 10, 47. doi:10.1038/s41419-018-1284-4. https://pubmed.ncbi.nlm.nih.gov/30718470/