Ppp1r1b, also known as Protein phosphatase 1 regulatory inhibitor subunit 1B, codes for multiple transcripts and two proteins, Darpp-32 and t-Darpp. Darpp-32 phosphorylation is upregulated by cAMP in dopamine-responsive brain tissues, modulating Protein Phosphatase 1 activity, which controls hundreds of phosphorylated proteins. PPP1R1B-knockout mice exhibit subtle learning defects [2].

In pancreatic cancer, loss of HIF1A increases PPP1R1B expression. EKPC mice with pancreas-specific deletion of HIF1A develop more advanced pancreatic neoplasias and PDACs with more invasion and metastasis. PPP1R1B promotes p53 degradation by stabilizing MDM2 phosphorylation at Ser166, and knockdown of PPP1R1B reduces the ability of pancreatic cancer cells to form lung metastases in mice [1]. In gastric cancer, the PPP1R1B-STARD3 chimeric fusion transcript, detected in 21.3% of primary human gastric cancers, promotes tumorigenesis through activation of PI3K/AKT signaling [3].

In summary, Ppp1r1b plays a crucial role in multiple biological processes and disease conditions. Gene-knockout mouse models have revealed its significance in cancer development, especially in pancreatic and gastric cancers, by influencing key cellular pathways related to tumor invasion, metastasis, and growth.

References:

1. Tiwari, Ashutosh, Tashiro, Kojiro, Dixit, Ajay, Provenzano, Paolo P, Bagchi, Anindya. 2020. Loss of HIF1A From Pancreatic Cancer Cells Increases Expression of PPP1R1B and Degradation of p53 to Promote Invasion and Metastasis. In Gastroenterology, 159, 1882-1897.e5. doi:10.1053/j.gastro.2020.07.046. https://pubmed.ncbi.nlm.nih.gov/32768595/

2. Avanes, Arabo, Lenz, Gal, Momand, Jamil. 2018. Darpp-32 and t-Darpp protein products of PPP1R1B: Old dogs with new tricks. In Biochemical pharmacology, 160, 71-79. doi:10.1016/j.bcp.2018.12.008. https://pubmed.ncbi.nlm.nih.gov/30552871/

3. Yun, S M, Yoon, K, Lee, S, Yang, H-K, Kim, S-J. 2013. PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling. In Oncogene, 33, 5341-7. doi:10.1038/onc.2013.472. https://pubmed.ncbi.nlm.nih.gov/24276243/