Targeting PRAS40: a novel therapeutic strategy for human diseases

Abstract

Proline-rich Akt substrate of 40 kD (PRAS40) is not only the substrate of protein kinase B (PKB/Akt), but also the binding protein of 14-3-3 protein. PRAS40 is expressed in a variety of tissues in vivo and has multiple phosphorylation sites, which its activity is closely related to phosphorylation. Studies have shown that PRAS40 is involved in regulating cell growth, cell apoptosis, oxidative stress, autophagy and angiogenesis, as well as various of signalling pathways such as mammalian target of mammalian target rapamycin (mTOR), protein kinase B (PKB/Akt), nuclear factor kappa-B(NF-κB), proto-oncogene serine/threonine-protein kinase PIM-1(PIM1) and pyruvate kinase M2 (PKM2). The interactive roles between PRAS40 and these signal proteins were analysed by bioinformatics in this paper. Moreover, it is of great necessity for analyse the important roles of PRAS40 in some human diseases including cardiovascular disease, ischaemia-reperfusion injury, neurodegenerative disease, cancer, diabetes and other metabolic diseases. Finally, the effects of miRNA on the regulation of PRAS40 function and the occurrence and development of PRAS40-related diseases are also discussed. Overall, PRAS40 is expected to be a drug target and provide a new treatment strategy for human diseases.

Keywords:

• PRAS40
• PIM1
• PKM2
• ischaemia-reperfusion injury
• cancer

Disclosure statement

The authors declare there are no conflicts of interest. This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Funding

This work was supported by the grants from the Scientific research project of Hunan Education Department [No. 16C1155], Hunan Provincial Natural Science Foundation [No. 2019JJ50424] and Science and technology project cultivation plan of Hunan University of Medicine (No.19KJPY06).