Pycr1-flox Mouse

PYCR1, pyrroline-5-carboxylate reductase 1, is the final enzyme in proline biosynthesis, converting pyrroline-5-carboxylate (P5C) to proline. Proline is involved in maintaining cell redox balance and preventing apoptosis. PYCR1 has been associated with multiple pathways and is emerging as an important target in oncology research [9,10]. Mouse models have been valuable for studying its function.

In cancer, PYCR1 has been found to play oncogenic roles. In colorectal cancer, under hypoxia, nuclear IGF1R phosphorylates PYCR1 at Tyrosine 135, promoting its binding to ELK4 and thus affecting gene transcription and tumor growth [1]. In liver cancer, PYCR1 promotes cell growth and metastasis by regulating IRS1 expression through lactylation modification [2]. In breast cancer, cancer-associated fibroblasts require PYCR1 for proline synthesis to deposit pro-tumorigenic extracellular matrix [3]. Similar tumor-promoting effects have been observed in pancreatic, bladder, papillary renal cell, and lung cancers [4,5,7,8]. In allergic asthma, PYCR1 is increased and promotes airway remodeling, and its knockout in mice reduces airway remodeling and EMT [6].

In conclusion, PYCR1 is essential for proline biosynthesis and has significant impacts on multiple disease areas, especially cancer and allergic asthma. Mouse models, including gene knockout models, have been crucial in revealing its roles in these biological processes and disease conditions, providing potential therapeutic targets for treatment.