Lypla2-KO Mouse

Lypla2, also known as APT2 (acyl protein thioesterase 2), is an enzyme involved in protein depalmitoylation. Protein depalmitoylation is the removal of thioester-linked long-chain fatty acids from cysteine residues in proteins, which is crucial for processes like membrane targeting, signaling, growth, and cell organization [2].

One key finding shows that in a mouse model, pharmacological inhibition of APT2 relieves the symptoms of inflammatory bowel disease (IBD). APT2 (Lypla2) depalmitoylates phosphorylated STAT3 (p-STAT3), enabling its translocation to the nucleus. This palmitoylation-depalmitoylation cycle enhances STAT3 activation and promotes TH17 cell differentiation. Overactivation of TH17 cells is associated with IBD, thus indicating that Lypla2 plays a role in the pathogenesis of IBD [1].

In conclusion, Lypla2 is important for the depalmitoylation process, especially in the regulation of STAT3-mediated TH17 cell differentiation. The study of Lypla2 using mouse models, like the pharmacological inhibition in the IBD-related study, has provided insights into its role in inflammatory diseases such as IBD, highlighting its potential as a therapeutic target.

References:

1. Zhang, Mingming, Zhou, Lixing, Xu, Yuejie, Linder, Maurine E, Lin, Hening. 2020. A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis. In Nature, 586, 434-439. doi:10.1038/s41586-020-2799-2. https://pubmed.ncbi.nlm.nih.gov/33029007/

2. Won, Sang Joon, Cheung See Kit, Melanie, Martin, Brent R. 2017. Protein depalmitoylases. In Critical reviews in biochemistry and molecular biology, 53, 83-98. doi:10.1080/10409238.2017.1409191. https://pubmed.ncbi.nlm.nih.gov/29239216/