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