Ppp2r5e-KO Mouse

Ppp2r5e, encoding the PP2A regulatory subunit B56ε, belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A (PP2A) is crucial for cellular signalling, playing a pivotal role in brain function and development. Ppp2r5e may be involved in regulating microtubule organization by interacting with microtubule crosslinking factor 1 (MTCL1) [3].

In cancer research, miR-19b directly negatively regulates Ppp2r5e in colorectal cancer (CRC) cells. Downregulation of Ppp2r5e mediates miR-19b-induced oncogenic effects, increasing cell viability, colonosphere formation, and cell migration, and also mediates miR-19b-induced 5-FU sensitivity in CRC cells [1]. In gastric cancer, miR-23a downregulates Ppp2r5e, and overexpression of Ppp2r5e reverses the negative effects of miR-23a on cell growth and apoptosis [2]. Downregulation of Ppp2r5e is also a common event in acute myeloid leukemia, affecting the oncogenic potential of leukemic cells [4]. In addition, a genetic polymorphism (rs1255722AA) in Ppp2r5e is associated with an increased risk of lung cancer in Chinese populations, and lung cancer tissues with this variant genotype have a lower mRNA level of Ppp2r5e [6]. In Alzheimer's disease, ApoE transcriptionally represses Ppp2r5e, reducing protein expression and disrupting the PPP2R5E-PP2AC complex, leading to decreased PP2A activity and potentially elevated Tau phosphorylation [5].

In conclusion, Ppp2r5e is a key regulatory subunit of PP2A, involved in important cellular signalling processes. Its dysregulation is associated with multiple diseases, especially cancers, where it may act as a tumour suppressor. Studies on Ppp2r5e contribute to understanding the pathogenesis of these diseases and may provide potential therapeutic targets.

References:

1. Santos, Andrea, Cristóbal, Ion, Caramés, Cristina, Rojo, Federico, García-Foncillas, Jesús. 2023. Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells. In International journal of molecular sciences, 24, . doi:10.3390/ijms24097779. https://pubmed.ncbi.nlm.nih.gov/37175484/

2. Liu, Xue, Liu, Qian, Fan, Yajie, Liu, Min, Tang, Hua. 2014. Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells. In FEBS letters, 588, 3160-9. doi:10.1016/j.febslet.2014.05.068. https://pubmed.ncbi.nlm.nih.gov/24997345/

3. Hyodo, Toshinori, Ito, Satoko, Asano-Inami, Eri, Chen, Dan, Senga, Takeshi. . A regulatory subunit of protein phosphatase 2A, PPP2R5E, regulates the abundance of microtubule crosslinking factor 1. In The FEBS journal, 283, 3662-3671. doi:10.1111/febs.13835. https://pubmed.ncbi.nlm.nih.gov/27521566/

4. Cristóbal, Ion, Cirauqui, Cristina, Castello-Cros, Remedios, Calasanz, María J, Odero, María D. 2013. Downregulation of PPP2R5E is a common event in acute myeloid leukemia that affects the oncogenic potential of leukemic cells. In Haematologica, 98, e103-4. doi:10.3324/haematol.2013.084731. https://pubmed.ncbi.nlm.nih.gov/23812941/

5. Theendakara, Veena, Bredesen, Dale E, Rao, Rammohan V. 2017. Downregulation of protein phosphatase 2A by apolipoprotein E: Implications for Alzheimer's disease. In Molecular and cellular neurosciences, 83, 83-91. doi:10.1016/j.mcn.2017.07.002. https://pubmed.ncbi.nlm.nih.gov/28720530/

6. Yang, Rongrong, Yang, Lei, Qiu, Fuman, Zhou, Yifeng, Lu, Jiachun. 2013. Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern Chinese. In PloS one, 8, e77285. doi:10.1371/journal.pone.0077285. https://pubmed.ncbi.nlm.nih.gov/24204789/