Ccdc115-KO Mouse

Ccdc115, short for coiled-coil domain containing 115, is an accessory component of vacuolar-ATPase. It plays diverse roles in multiple biological processes. Ccdc115 is involved in pathways such as autophagy, Hippo signalling, and is associated with cell proliferation, viral entry, and protein glycosylation [1,2,4]. It also has implications in iron and heme trafficking in erythroid cells and may be a driver in clonal hematopoiesis [5,6].

In autophagy, Ccdc115 inhibits autophagy-mediated degradation of yes-associated protein (YAP) under starvation. It interacts with the HOPS complex, competing with STX17, thus preventing the fusion of autophagosomes with lysosomes and promoting cell proliferation in nutrient-restricted conditions [1]. Genome-wide CRISPR screens identified Ccdc115 as an essential gene for influenza A virus entry and regulation of V-type ATPase assembly [2]. In liver cancer, its increased expression correlates with poor prognosis and affects cancer cell proliferation, metastasis, and sorafenib resistance, being involved in the PI3K-Akt pathway [3]. Ccdc115 deficiency causes a disorder of Golgi homeostasis with abnormal protein glycosylation, presenting symptoms like hepatosplenomegaly, abnormal copper metabolism, and neurological symptoms [4].

In summary, Ccdc115 is crucial in processes like autophagy, viral infection, and cell proliferation. Its role in diseases such as liver cancer, glycosylation disorders, and fatty liver disease has been revealed through various studies. Understanding Ccdc115's functions via model-based research, especially gene-knockout studies, could potentially provide new strategies for treating related diseases [1-3,5,9].

References:

1. Feng, Hui, Liu, Xiao, Zhou, Chenqian, Teng, Junlin, Zheng, Pengli. 2023. CCDC115 inhibits autophagy-mediated degradation of YAP to promote cell proliferation. In FEBS letters, 597, 618-630. doi:10.1002/1873-3468.14575. https://pubmed.ncbi.nlm.nih.gov/36650560/

2. Li, Bo, Clohisey, Sara M, Chia, Bing Shao, Baillie, J Kenneth, Hacohen, Nir. 2020. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. In Nature communications, 11, 164. doi:10.1038/s41467-019-13965-x. https://pubmed.ncbi.nlm.nih.gov/31919360/

3. Su, Chang, Yang, Jing-Cheng, Rong, Zheng, Zhao, Ming-Gao, Yang, Le. 2023. Identification of CCDC115 as an adverse prognostic biomarker in liver cancer based on bioinformatics and experimental analyses. In Heliyon, 9, e19233. doi:10.1016/j.heliyon.2023.e19233. https://pubmed.ncbi.nlm.nih.gov/37674842/

4. Jansen, Jos C, Cirak, Sebahattin, van Scherpenzeel, Monique, Marquardt, Thorsten, Lefeber, Dirk J. 2016. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation. In American journal of human genetics, 98, 310-21. doi:10.1016/j.ajhg.2015.12.010. https://pubmed.ncbi.nlm.nih.gov/26833332/

5. Sobh, Amin, Loguinov, Alex, Zhou, Jie, Fraenkel, Paula G, Vulpe, Christopher D. 2020. Genetic screens reveal CCDC115 as a modulator of erythroid iron and heme trafficking. In American journal of hematology, 95, 1085-1098. doi:10.1002/ajh.25899. https://pubmed.ncbi.nlm.nih.gov/32510613/

6. Bernstein, Nicholas, Spencer Chapman, Michael, Nyamondo, Kudzai, Cohen, Robert L, Nangalia, Jyoti. 2024. Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis. In Nature genetics, 56, 1147-1155. doi:10.1038/s41588-024-01755-1. https://pubmed.ncbi.nlm.nih.gov/38744975/