Cobll1-KO Mouse

Cobll1, also known as cordon-bleu WH2 repeat protein like 1, has been implicated in multiple biological processes and diseases. It may play a role in cell morphogenesis as it has an actin-binding domain. In signaling pathways, it is associated with the regulation of drug resistance-related pathways and NF-κB activation [3,4]. It is also linked to processes like hematopoiesis during vertebrate embryogenesis [1].

In chronic myeloid leukemia (CML), Cobll1 affects blast crisis progression and tyrosine kinase inhibitor (TKI) resistance. It increases IKKγ stability, leading to NF-κB activation and reduced nilotinib-dependent apoptosis. High expression of Cobll1 confers drug resistance in CML cell lines and patient samples, and its expression is dramatically increased in blast crisis compared to the chronic phase, correlating with a poor survival rate. Similar interactions among Cobll1, PACSIN2, and SH3BP1 control hematopoiesis during embryogenesis [1,4].

In advanced prostate cancer, Cobll1 is highly induced by the androgen receptor (AR) in castration-resistant prostate cancer model cells. It is involved in cancer cell morphogenesis to a neuron-like shape, promoting cell growth and migration. Nuclear Cobll1 interacts with AR to enhance complex formation with CDK1 and facilitates AR phosphorylation for genomic binding [3].

In gestational diabetes, the COBLL1 rs7607980 gene polymorphism was not found to be a significant risk factor [2]. In obesity, COBLL1 genetic variants interact with dietary fat intake to modulate the incidence of obesity in a sex-dependent manner [5].

In conclusion, Cobll1 is involved in various biological functions such as cell morphogenesis, hematopoiesis, and regulation of drug-resistance pathways. Its study in models like those of CML and advanced prostate cancer has provided insights into disease mechanisms, suggesting it could be a potential biomarker and therapeutic target in these diseases.

References:

1. Park, Kibeom, Yoo, Hee-Seop, Oh, Chang-Kyu, Lee, Yoonsung, Kim, Dong-Wook. 2022. Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia. In Cancer medicine, 11, 4005-4020. doi:10.1002/cam4.4727. https://pubmed.ncbi.nlm.nih.gov/35352878/

2. Ustianowski, Przemyslaw, Malinowski, Damian, Czerewaty, Michał, Dziedziejko, Violetta, Pawlik, Andrzej. 2022. COBLL1 and IRS1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes. In Biomedicines, 10, . doi:10.3390/biomedicines10081933. https://pubmed.ncbi.nlm.nih.gov/36009479/

3. Takayama, Ken-Ichi, Suzuki, Takashi, Fujimura, Tetsuya, Takahashi, Satoru, Inoue, Satoshi. 2018. COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer. In Proceedings of the National Academy of Sciences of the United States of America, 115, 4975-4980. doi:10.1073/pnas.1721957115. https://pubmed.ncbi.nlm.nih.gov/29686105/

4. Han, S H, Kim, S-H, Kim, H-J, Kim, H, Kim, D-W. 2017. Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia. In Leukemia, 31, 1532-1539. doi:10.1038/leu.2017.72. https://pubmed.ncbi.nlm.nih.gov/28232743/

5. Kwak, Junkyung, Shin, Dayeon. 2023. Gene-Nutrient Interactions in Obesity: COBLL1 Genetic Variants Interact with Dietary Fat Intake to Modulate the Incidence of Obesity. In International journal of molecular sciences, 24, . doi:10.3390/ijms24043758. https://pubmed.ncbi.nlm.nih.gov/36835164/