Interactions between 14-3-3 Proteins and Actin Cytoskeleton and Its Regulation by microRNAs and Long Non-Coding RNAs in Cancer

Abstract

14-3-3s are a family of structurally similar proteins that bind to phosphoserine or phosphothreonine residues, forming the central signaling hub that coordinates or integrates various cellular functions, thereby controlling many pathways important in cancer, cell motility, cell death, cytoskeletal remodeling, neuro-degenerative disorders and many more. Their targets are present in all cellular compartments, and when they bind to proteins they alter their subcellular localization, stability, and molecular interactions with other proteins. Changes in environmental conditions that result in altered homeostasis trigger the interaction between 14-3-3 and other proteins to retrieve or rescue homeostasis. In circumstances where these regulatory proteins are dysregulated, it leads to pathological conditions. Therefore, deeper understanding is needed on how 14-3-3 proteins bind, and how these proteins are regulated or modified. This will help to detect disease in early stages or design inhibitors to block certain pathways. Recently, more research has been devoted to identifying the role of MicroRNAs, and long non-coding RNAs, which play an important role in regulating gene expression. Although there are many reviews on the role of 14-3-3 proteins in cancer, they do not provide a holistic view of the changes in the cell, which is the focus of this review. The unique feature of the review is that it not only focuses on how the 14-3-3 subunits associate and dissociate with their binding and regulatory proteins, but also includes the role of micro-RNAs and long non-coding RNAs and how they regulate 14-3-3 isoforms. The highlight of the review is that it focuses on the role of 14-3-3, actin, actin binding proteins and Rho GTPases in cancer, and how this complex is important for cell migration and invasion. Finally, the reader is provided with super-resolution high-clarity images of each subunit of the 14-3-3 protein family, further depicting their distribution in HeLa cells to illustrate their interactions in a cancer cell.