Lipin-1 stability and its adipogenesis functions are regulated in contrasting ways by AKT1 and LKB1

Abstract

Lipin‐1 is a protein that plays a critical role in many cellular functions. At molecular level, it acts as a phosphatidic acid phosphohydrolase and a transcriptional coactivator. The functions of lipin‐1 are largely dependent upon its subcellular localization, post‐translational modifications like phosphorylation and acetylation, and also on its interaction with other proteins such as 14‐3‐3. However, the kinases and phosphatases that are responsible for these post translational modifications are not entirely known. Using bioinformatics and other biochemical approaches, we demonstrate lipin‐1 as a novel target for AKT1 and LKB1. While AKT1 stabilizes lipin‐1, LKB1 causes its degradation. Interestingly, our findings further show that lipin‐1 enhances AKT1 activity as can be seen by increased phosphorylation of the substrates of AKT1. Taken together, our results suggest that lipin‐1 plays an important role in the regulation of PI3K‐AKT‐mTOR pathway, which is dysregulated in majority of cancers. Therefore, understating the role of lipin‐1 may provide new and important insights into the regulation and functions of the PI3K‐mTOR pathway, which is one of the major targets for anti‐cancer drug development strategies.