Rps6kb1, also known as ribosomal protein S6 kinase B1 or p70S6K1, is a key kinase involved in protein translation. It is a downstream effector of the MTOR (mechanistic target of rapamycin kinase) pathway, which is crucial for regulating cell growth, metabolism, and autophagy [1,2,3,4,5,6,9].

In the context of non-alcoholic fatty liver disease (NAFLD), fructose-induced hepatic steatosis is promoted by Rps6kb1-driven augmentation of hepatic protein synthesis, leading to endoplasmic reticulum (ER)-stress and upregulation of pro-lipogenic genes [10]. In mumps virus infection, Rps6kb1 negatively regulates virus replication and transcription, likely through its interaction with the viral P protein [7]. In non-small cell lung cancer (NSCLC), hyperphosphorylation of Rps6kb1 rather than overexpression is an independent unfavorable prognostic marker, and its dephosphorylation suppresses cell proliferation and promotes apoptosis [8].

In conclusion, Rps6kb1 is an important component of the MTOR pathway, playing significant roles in processes such as protein synthesis, viral replication, and cancer prognosis. The study of Rps6kb1 using various research models has provided insights into diseases like NAFLD, viral infections, and NSCLC, which may help in developing new therapeutic strategies for these conditions.

References:

1. Park, Hee-Seon, Song, Ji-Won, Park, Jin-Ho, Won, Young-Suk, Kwon, Hyo-Jung. 2020. TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. In Autophagy, 17, 2549-2564. doi:10.1080/15548627.2020.1834711. https://pubmed.ncbi.nlm.nih.gov/33190588/

2. Foerster, Elisabeth G, Mukherjee, Tapas, Cabral-Fernandes, Liliane, Girardin, Stephen E, Philpott, Dana J. 2021. How autophagy controls the intestinal epithelial barrier. In Autophagy, 18, 86-103. doi:10.1080/15548627.2021.1909406. https://pubmed.ncbi.nlm.nih.gov/33906557/

3. Devis-Jauregui, Laura, Eritja, Núria, Davis, Meredith Leigh, Matias-Guiu, Xavier, Llobet-Navàs, David. 2020. Autophagy in the physiological endometrium and cancer. In Autophagy, 17, 1077-1095. doi:10.1080/15548627.2020.1752548. https://pubmed.ncbi.nlm.nih.gov/32401642/

4. Liu, Kunpeng, Qiu, Dongbo, Liang, Xue, Qin, Yunfei, Zhang, Qi. 2021. Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy. In Autophagy, 18, 860-876. doi:10.1080/15548627.2021.1961072. https://pubmed.ncbi.nlm.nih.gov/34382907/

5. Hwang, Hui-Yun, Shim, Joong Sup, Kim, Dasol, Kwon, Ho Jeong. 2020. Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein. In Autophagy, 17, 2783-2799. doi:10.1080/15548627.2020.1841953. https://pubmed.ncbi.nlm.nih.gov/33124469/

6. Niu, Jianfang, Yan, Taiqiang, Guo, Wei, Lou, Jingbing, Guo, Lei. 2022. The COPS3-FOXO3 positive feedback loop regulates autophagy to promote cisplatin resistance in osteosarcoma. In Autophagy, 19, 1693-1710. doi:10.1080/15548627.2022.2150003. https://pubmed.ncbi.nlm.nih.gov/36451342/

7. Briggs, Kelsey, Wang, Leyi, Nagashima, Kaito, Tripp, Ralph A, He, Biao. 2020. Regulation of Mumps Virus Replication and Transcription by Kinase RPS6KB1. In Journal of virology, 94, . doi:10.1128/JVI.00387-20. https://pubmed.ncbi.nlm.nih.gov/32295907/

8. Chen, Bojiang, Yang, Lan, Zhang, Rui, Chen, Hong, Tang, Huairong. 2017. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients. In PloS one, 12, e0182891. doi:10.1371/journal.pone.0182891. https://pubmed.ncbi.nlm.nih.gov/28792981/

9. Yan, Guokai, Li, Xiuzhi, Zheng, Zilong, Zhong, Qing, Yan, Xianghua. 2022. KAT7-mediated CANX (calnexin) crotonylation regulates leucine-stimulated MTORC1 activity. In Autophagy, 18, 2799-2816. doi:10.1080/15548627.2022.2047481. https://pubmed.ncbi.nlm.nih.gov/35266843/

10. Raza, Sana, Shahi, Ambuj, Medhe, Pratik, Chakravarti, Bandana, Sinha, Rohit Anthony. 2023. Fructose-induced perturbation in cellular proteostasis via RPS6KB1 promotes hepatic steatosis. In Biochimica et biophysica acta. Molecular cell research, 1871, 119597. doi:10.1016/j.bbamcr.2023.119597. https://pubmed.ncbi.nlm.nih.gov/37741573/