Cbl-KO Mouse

Cbl, short for Casitas B lineage lymphoma, is a multifunctional protein with E3 ubiquitin ligase activity. It can degrade diverse proteins and plays a key role in different cell pathways, mainly related to cancer onset and progression, hematopoietic development, T cell receptor regulation, and muscle atrophy [2,3,5]. In plants, the CBL-CIPK network, where CBL is a calcineurin B-like protein, mediates Ca²⁺-related signaling pathways in response to abiotic and biotic stimuli [6].

In muscle atrophy, Cbl-b ubiquitinates and induces the degradation of IRS-1, a key intermediate in the IGF-1 signaling, which is crucial in unloading muscle atrophy in spaceflight and bedridden patients [1]. In cancer, somatic CBL mutations have been reported in various malignancies, and germline CBL mutations configure the so-called CBL syndrome, a cancer-predisposing condition [2]. Also, c-Cbl is considered a critical regulator and potential target in angiogenesis and human solid organ tumors [3]. The E3 ubiquitin ligase Cbl-b is a novel target in immune-oncology, modulating immune responses by facilitating ubiquitination and degradation of key signaling proteins [4].

In conclusion, Cbl is essential in multiple biological processes. Its role in muscle atrophy, cancer, angiogenesis, and immune-oncology has been revealed through various studies. Understanding Cbl function through gene-based research models can potentially provide new therapeutic strategies for related diseases.

References:

1. Nikawa, Takeshi, Ishidoh, Kazumi. 2020. Ubiquitin ligase Cbl-b and inhibitory Cblin peptides. In Biochimica et biophysica acta. Proteins and proteomics, 1868, 140495. doi:10.1016/j.bbapap.2020.140495. https://pubmed.ncbi.nlm.nih.gov/32663526/

2. Leardini, Davide, Messelodi, Daria, Muratore, Edoardo, Pession, Andrea, Masetti, Riccardo. 2022. Role of CBL Mutations in Cancer and Non-Malignant Phenotype. In Cancers, 14, . doi:10.3390/cancers14030839. https://pubmed.ncbi.nlm.nih.gov/35159106/

3. Lyle, Chimera L, Belghasem, Mostafa, Chitalia, Vipul C. 2019. c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis. In Cells, 8, . doi:10.3390/cells8050498. https://pubmed.ncbi.nlm.nih.gov/31126146/

4. Fusco, Riccardo, Saedi, Zeinab, Capriello, Imma, Lubskyy, Andriy, Dömling, Alexander. 2024. CBL-B - An upcoming immune-oncology target. In Expert opinion on therapeutic patents, 35, 47-64. doi:10.1080/13543776.2024.2412567. https://pubmed.ncbi.nlm.nih.gov/39582379/

5. Ren, Jiaqi, Lv, Linlin, Tao, Xufeng, Dong, Deshi, Liu, Jing. 2024. The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies. In Frontiers in pharmacology, 15, 1432545. doi:10.3389/fphar.2024.1432545. https://pubmed.ncbi.nlm.nih.gov/39130630/

6. Yu, Qinyang, An, Lijia, Li, Wenli. 2013. The CBL-CIPK network mediates different signaling pathways in plants. In Plant cell reports, 33, 203-14. doi:10.1007/s00299-013-1507-1. https://pubmed.ncbi.nlm.nih.gov/24097244/