14-3-3 proteins as potential therapeutic targets

• Authors: Jing Zhao, Emory University; Cheryl L. Meyerkord, Emory University; Yuhong Du, Emory University; Fadlo Khuri, Emory University; Haian Fu, Emory University
• Journal Title: Seminars in Cell and Developmental Biology
• Volume: Volume 22, Number 7
• Publisher: Elsevier: 12 months | 2011-09, Pages 705-712
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.semcdb.2011.09.012
• Subjects: Health Sciences, Pharmacology; Health Sciences, Oncology
• Keywords: 14-3-3 inhibitor; stabilizer

Abstract

The 14-3-3 family of phosphoserine/phosphothreonine-binding proteins dynamically regulates the activity of client proteins in various signaling pathways that control diverse physiological and pathological processes. In response to environmental cues, 14-3-3 proteins orchestrate the highly regulated flow of signals through complex networks of molecular interactions to achieve well-controlled physiological outputs, such as cell proliferation or differentiation. Accumulating evidence now supports the concept that either an abnormal state of 14-3-3 protein expression, or dysregulation of 14-3-3/client protein interactions, contributes to the development of a large number of human diseases. In particular, clinical investigations in the field of oncology have demonstrated a correlation between upregulated 14-3-3 levels and poor survival of cancer patients. These studies highlight the rapid emergence of 14-3-3 proteins as a novel class of molecular target for potential therapeutic intervention. The current status of 14-3-3 modulator discovery is discussed.