Ppp1ca, encoding Protein phosphatase 1 catalytic subunit alpha, is a key component of the PP1 complex. It is involved in regulating diverse cellular processes such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription [6]. It participates in multiple pathways, like the WNK/SPAK pathway in the context of blood pressure regulation, and the PPP1CA/YAP/GS/Gln/mTORC1 pathway in retinal Müller cell activation [4,5]. Genetic models, such as knockout models, are valuable for studying its functions.

In osteoporosis, CARM1-mediated arginine methylation of PPP1CA at R23 affects glucose metabolism, promoting osteogenic differentiation and inhibiting osteoclastic differentiation by regulating the dephosphorylation of AKT-T450 and AMPK-T172, and up-regulating glycolytic flux [1]. In intervertebral disc degeneration, SUV39H2-mediated lysine methylation of PPP1CA at K141 disrupts TFEB-dependent autophagy, leading to NPC senescence and IDD progression [2]. In clear cell renal cell carcinoma, the peptide PDHK1-241aa encoded by circPDHK1 interacts with PPP1CA, inhibits AKT dephosphorylation, and activates the AKT-mTOR signaling pathway to promote cancer progression [3].

In summary, Ppp1ca plays essential roles in various biological processes and disease conditions. Through gene knockout and other functional studies, it has been revealed that Ppp1ca is crucial in areas such as osteoporosis, intervertebral disc degeneration, and clear cell renal cell carcinoma, providing insights into potential therapeutic strategies for these diseases.

References:

1. Zhang, Lu, Jiao, Guangjun, You, Yunhao, Meng, Chunyang, Chen, Yunzhen. . Arginine methylation of PPP1CA by CARM1 regulates glucose metabolism and affects osteogenic differentiation and osteoclastic differentiation. In Clinical and translational medicine, 13, e1369. doi:10.1002/ctm2.1369. https://pubmed.ncbi.nlm.nih.gov/37649137/

2. Liang, Huaizhen, Luo, Rongjin, Li, Gaocai, Song, Yu, Yang, Cao. 2023. Lysine methylation of PPP1CA by the methyltransferase SUV39H2 disrupts TFEB-dependent autophagy and promotes intervertebral disc degeneration. In Cell death and differentiation, 30, 2135-2150. doi:10.1038/s41418-023-01210-4. https://pubmed.ncbi.nlm.nih.gov/37605006/

3. Huang, Bo, Ren, Junwu, Ma, Qiang, Wang, Yongquan, Xiao, Bin. 2024. A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway. In Molecular cancer, 23, 34. doi:10.1186/s12943-024-01940-0. https://pubmed.ncbi.nlm.nih.gov/38360682/

4. Guo, Yang, Cang, Xiaomin, Zhu, Linling, Wang, Xueqin, Song, E. 2021. PPP1CA/YAP/GS/Gln/mTORC1 pathway activates retinal Müller cells during diabetic retinopathy. In Experimental eye research, 210, 108703. doi:10.1016/j.exer.2021.108703. https://pubmed.ncbi.nlm.nih.gov/34280391/

5. Grimm, P Richard, Tatomir, Anamaria, Rosenbaek, Lena L, Fenton, Robert A, Welling, Paul A. 2023. Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure. In The Journal of clinical investigation, 133, . doi:10.1172/JCI158498. https://pubmed.ncbi.nlm.nih.gov/37676724/

6. Wang, Xiaoman, Sun, Jiaan, Fu, Chong, Liu, Chang. 2023. Generation of a PPP1CA knockout human pluripotent stem cell line via Nuclease technology. In Stem cell research, 69, 103077. doi:10.1016/j.scr.2023.103077. https://pubmed.ncbi.nlm.nih.gov/36965407/