Arrb1, also known as arrestin beta 1, is a multifunctional adaptor protein. It is involved in various cellular functions, often acting as a molecular scaffold. It participates in signaling pathways such as those related to G protein-coupled receptors (GPCRs), and is crucial for processes like autophagy, protein maturation, and metabolic reprogramming [1,2,6].

In mouse models, Arrb1 deficiency has provided insights into its role in different diseases. In hepatocellular carcinoma (HCC) related to the hepatitis B virus X protein (HBx), Arrb1 knockout suppressed HBx-induced carcinogenesis and blocked autophagic flux [1]. In non-alcoholic steatohepatitis (NASH), Arrb1-knockout mice showed accelerated disease development, highlighting its role in NASH progression [2]. In acetaminophen-induced liver injury, systemic Arrb1-KO mice were more susceptible to hepatotoxicity, demonstrating its protective role [3]. In gallbladder cancer, knockdown of Arrb1 in vitro and in vivo experiments showed that it enhanced cancer cell proliferation, migration, and invasion [4]. In intervertebral disc degeneration (IVDD), knockdown of Arrb1 in rat nucleus pulposus cells aggravated extracellular matrix degradation and apoptosis, while overexpression reversed these effects [5].

In conclusion, Arrb1 plays essential roles in multiple biological processes and diseases. Studies using gene knockout mouse models have revealed its significance in liver-related diseases like HCC, NASH, and acetaminophen-induced liver injury, as well as in gallbladder cancer and IVDD. These findings suggest that Arrb1 could be a potential therapeutic target for these diseases.

References:

1. Lei, Yiming, Xu, Xuan, Liu, Huiling, Yang, Yidong, Wu, Bin. 2021. HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G1/S cycle. In Autophagy, 17, 4423-4441. doi:10.1080/15548627.2021.1917948. https://pubmed.ncbi.nlm.nih.gov/33866937/

2. Zhang, Zechuan, Xu, Xiaoliang, Tian, Wenfang, Yu, Hailong, Sun, Beicheng. 2019. ARRB1 inhibits non-alcoholic steatohepatitis progression by promoting GDF15 maturation. In Journal of hepatology, 72, 976-989. doi:10.1016/j.jhep.2019.12.004. https://pubmed.ncbi.nlm.nih.gov/31857195/

3. Luo, Yujun, Lei, Yiming, Zhou, Haoxiong, Xu, Chengfang, Wu, Bin. 2024. ARRB1 downregulates acetaminophen-induced hepatoxicity through binding to p-eIF2α to inhibit ER stress signaling. In Cell biology and toxicology, 40, 1. doi:10.1007/s10565-024-09842-z. https://pubmed.ncbi.nlm.nih.gov/38252352/

4. Zhang, Xudong, Kong, Zhijun, Xu, Xiaoliang, Zhu, Chunfu, Qin, Xihu. 2021. ARRB1 Drives Gallbladder Cancer Progression by Facilitating TAK1/MAPK Signaling Activation. In Journal of Cancer, 12, 1926-1935. doi:10.7150/jca.53325. https://pubmed.ncbi.nlm.nih.gov/33753990/

5. Dan, Xuejian, Gu, Xiaochuan, Zi, Ying, Yu, Yan, Ma, Bin. 2024. ARRB1 inhibits extracellular matrix degradation and apoptosis of nucleus pulposus cells by promoting autophagy and attenuates intervertebral disc degeneration. In Biochimica et biophysica acta. Molecular cell research, 1871, 119769. doi:10.1016/j.bbamcr.2024.119769. https://pubmed.ncbi.nlm.nih.gov/38838859/

6. Mamouni, Kenza, Kim, Jeongheun, Lokeshwar, Bal L, Kallifatidis, Georgios. 2021. ARRB1 Regulates Metabolic Reprogramming to Promote Glycolysis in Stem Cell-Like Bladder Cancer Cells. In Cancers, 13, . doi:10.3390/cancers13081809. https://pubmed.ncbi.nlm.nih.gov/33920080/