Mechanisms of the 14-3-3 Protein Function: Regulation of Protein Function Through Conformational Modulation

Abstract

Many aspects of protein function regulation require specific protein-protein interactions to carry out the exact biochemical and cellular functions. The highly conserved members of the 14-3-3 protein family mediate such interactions and through binding to hundreds of other proteins provide multitude of regulatory functions, thus playing key roles in many cellular processes. The 14-3-3 protein binding can affect the function of the target protein in many ways including the modulation of its enzyme activity, its subcellular localization, its structure and stability, or its molecular interactions. In this minireview, we focus on mechanisms of the 14-3-3 protein-dependent regulation of three important 14-3-3 binding partners: yeast neutral trehalase Nth1, regulator of G-protein signaling 3 (RGS3), and phosducin.

Prospecting Biomarkers for Diagnostic and Therapeutic Approaches in Pythiosis

“…Finally, spot 19 identified the 14-3-3 protein epsilon, which is highly conserved in eukaryotes and abundant in phospho-serine/threonine binding proteins [96][97][98]. The 14-3-3 epsilon plays important roles in the cell cycle, coordinating cell progression and acting on signal transformation networks through bonds with other proteins [97,99]; these bonds affect the conformation and function of target proteins [98]. In Paracoccidioides brasiliensis, the 14-3-3 protein (Pb14-3-3) is a critical antigen [75], which is highly expressed in virulent isolates and works as an adhesin [100].…”

Proteomic and Immunological Identification of Diagnostic Antigens from Spirometra erinaceieuropaei Plerocercoid

“…Another potential S. erinaceieuropaei antigen identified in the present study, 14-3-3 protein, was previously identified in several unicellular and multicellular parasites [ 47 ]. The 14-3-3 proteins are a family of highly conserved proteins that are widely expressed in many eukaryotic organisms and has been shown to play a role in metabolism, signal transduction networks, stress conditions, cell cycle regulation, control of apoptosis and cellular organelle trafficking [ 48 – 50 ]. In the field of parasitology, 14-3-3 protein has been assumed to play an important role in parasite proliferation and survival [ 47 , 51 ].…”

Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom

“…However, a direct interaction was recently demonstrated between 14-3-3 and Rac1 that is facilitated by the AKT-mediated phosphorylation of Rac1 at S71 [ 324 ]. A similar interaction between 14-3-3 proteins and RhoA has not been shown yet, but it is interesting to note that both RhoA and RacE share the RPLpSYP motif with Rac1, which is very close to the type I consensus motif for the binding of 14-3-3 proteins [ 325 ], suggesting that S73 phosphorylation could regulate the interaction of RhoA with 14-3-3 proteins. In Dictyostelium and humans alike, 14-3-3 proteins bind directly to the tail of nonmuscle myosin II and inhibit its assembly into bipolar filaments, which increases the soluble fraction of myosin in the cell and promotes myosin turnover [ 309 ].…”