PEBP1/RKIP: from multiple functions to a common role in cellular processes

TL;DR

PEBP1/RKIP is a multifunctional protein involved in key cellular processes and signaling pathways, with implications in cancer, neurodegeneration, and metabolic diseases, acting as a modulator of molecular interactions.

Contribution

This review consolidates current knowledge on PEBP1's diverse roles and proposes it as a central modulator of signal transduction and cellular organization.

Findings

PEBP1 inhibits multiple kinase signaling pathways.

PEBP1 interacts with various small ligands and cellular structures.

PEBP1's role extends across cancer, neurodegeneration, and metabolic diseases.

Abstract

PEBPs (PhosphatidylEthanolamine Binding Proteins) form a protein family widely present in the living world since they are encountered in microorganisms, plants and animals. In all organisms PEBPs appear to regulate important mechanisms that govern cell cycle, proliferation, differentiation and motility. In humans, three PEBPs have been identified, namely PEBP1, PEBP2 and PEBP4. PEBP1 and PEBP4 are the most studied as they are implicated in the development of various cancers. PEBP2 is specific of testes in mammals and was essentially studied in rats and mice where it is very abundant. A lot of information has been gained on PEBP1 also named RKIP (Raf Kinase Inhibitory protein) due to its role as a metastasis suppressor in cancer. PEBP1 was also demonstrated to be implicated in Alzheimers disease, diabetes and nephropathies. Furthermore, PEBP1 was described to be involved in many cellular processes, among them are signal transduction, inflammation, cell cycle, proliferation, adhesion, differentiation, apoptosis, autophagy, circadian rhythm and mitotic spindle checkpoint. On the molecular level, PEBP1 was shown to regulate several signaling pathways such as Raf/MEK/ERK, NFkB, PI3K/Akt/mTOR, p38, Notch and Wnt. PEBP1 acts by inhibiting most of the kinases of these signaling cascades. Moreover, PEBP1 is able to bind to a variety of small ligands such as ATP, phospholipids, nucleotides, flavonoids or drugs. Considering PEBP1 is a small cytoplasmic protein (21kDa), its involvement in so many diseases and cellular mechanisms is amazing. The aim of this review is to highlight the molecular systems that are common to all these cellular mechanisms in order to decipher the specific role of PEBP1. Recent discoveries enable us to propose that PEBP1 is a modulator of molecular interactions that control signal transduction during membrane and cytoskeleton reorganization.