Cand1, short for Cullin-associated and neddylation-dissociated protein 1, is a crucial regulator in the assembly and disassembly of cullin-RING ubiquitin ligases (CRLs), especially those like the SCF (SKP1-CUL1-F box protein) complex. CRLs are involved in protein ubiquitination and degradation, a process fundamental to numerous cellular functions such as cell cycle regulation, signal transduction, and apoptosis [2,4,5,6]. Genetic models, like gene knockout (KO) mouse models, have been valuable in studying Cand1's function.

In non-alcoholic fatty liver disease (NAFLD), Cand1 levels are reduced in the livers of male patients and high-fat diet-fed male mice. Hepatocyte-specific knockout of Cand1 exacerbates HFD-induced liver injury, while hepatocyte-specific knockin ameliorates the pathological changes. Mechanistically, Cand1 deficiency enhances the assembly of Cullin1, FBXO42, and ACAA2 complexes, promoting ACAA2's ubiquitinated degradation [1]. In prostate cancer, immunohistochemical analyses showed higher Cand1 protein levels in cancerous areas compared to benign ones. Knockdown of Cand1 in prostate cancer cell lines reduced cell viability and proliferation and increased apoptosis [3].

In conclusion, Cand1 is essential for regulating the assembly of CRLs, thereby influencing protein degradation pathways. Mouse models with Cand1 knockout or knockdown have revealed its role in diseases like NAFLD and prostate cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Huang, Xiang, Liu, Xin, Li, Xingda, Yang, Baofeng, Pan, Zhenwei. 2023. Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2. In Nature communications, 14, 4620. doi:10.1038/s41467-023-40327-5. https://pubmed.ncbi.nlm.nih.gov/37528093/

2. Xie, Yuan, Zhao, Minglei. . CAND1 orchestrates CRLs through rock and roll. In Cell, 186, 1817-1818. doi:10.1016/j.cell.2023.04.001. https://pubmed.ncbi.nlm.nih.gov/37116466/

3. Eigentler, Andrea, Tymoszuk, Piotr, Zwick, Johanna, Klocker, Helmut, Heidegger, Isabel. 2020. The Impact of Cand1 in Prostate Cancer. In Cancers, 12, . doi:10.3390/cancers12020428. https://pubmed.ncbi.nlm.nih.gov/32059441/

4. Baek, Kheewoong, Scott, Daniel C, Henneberg, Lukas T, Mann, Matthias, Schulman, Brenda A. 2023. Systemwide disassembly and assembly of SCF ubiquitin ligase complexes. In Cell, 186, 1895-1911.e21. doi:10.1016/j.cell.2023.02.035. https://pubmed.ncbi.nlm.nih.gov/37028429/

5. Li, Lihong, Garsamo, Melaku, Yuan, Jing, Zhou, Yun, Liu, Xing. 2022. CAND1 is required for pollen viability in Arabidopsis thaliana-a test of the adaptive exchange hypothesis. In Frontiers in plant science, 13, 866086. doi:10.3389/fpls.2022.866086. https://pubmed.ncbi.nlm.nih.gov/35968124/

6. Shaaban, Mohammed, Clapperton, Julie A, Ding, Shan, Skehel, J Mark, Enchev, Radoslav I. 2023. Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange. In Molecular cell, 83, 2332-2346.e8. doi:10.1016/j.molcel.2023.05.034. https://pubmed.ncbi.nlm.nih.gov/37339624/