60 YEARS OF POMC: POMC: the consummate peptide hormone precursor.

editorial 60 years of POMC a j l clark and p lowry 56:4 E1–E2 Proopiomelanocortin (POMC) has been at the forefront of molecular endocrinology for the past 60 years, and the concepts derived from POMC research have led the way in understanding a wide range of endocrine systems. In this issue, we celebrate this enormous body of work with contributions from an outstanding faculty of contributors, many of whom have led these discoveries. The story begins approximately 60 years ago when Li and colleagues reported purifying and sequencing ACTH (Li et al. 1955, Dixon & Li 1956). They and others subsequently reported purification of α-and β-MSH; however, it was with the discovery of β-LPH that the prohormone theory was advanced: that a single peptide precursor molecule could contain several independent biologically active members. These discoveries, and his contributions to them, are reviewed by Phil Lowry (Lowry 2016). A key discovery was that of β-endorphin: Derek Smyth recalls his work and the events surrounding this (Smyth 2016). Confirmation of the single-precursor concept was provided by the cloning of the POMC gene by Nakanishi and coworkers; work reviewed by Adrian Clark (Clark 2016). Cloning of POMC additionally revealed undiscovered N-terminal components of this precursor whose potential biological function is reviewed by Andrew Bicknell (Bicknell 2016). Understanding the processing of these peptides has provided fundamental models that are observed extensively in peptide biology. Specifically, cleavage of POMC into its active components requires the action of a novel series of enzymes, the prohormone convertases, reviewed by Michel Chretien and Majambu Mbikay (Chretien & Mbikay 2016). Further processing of POMC products by C-terminal amidation revealed the class of peptidylglycine α-amidating monooxygenase enzymes whose far wider role continues to be an active area of research and is reviewed by Dhivya Kumar and colleagues (Kumar et al. 2016). The subsequent trafficking, sorting, and storage of POMC products before secretion has also contributed significantly to our knowledge of the broader aspects of this process and is reviewed by Peng Loh and colleagues (Cawley et al. 2016). Cloning of the POMC gene confirmed the highly tissue-specific nature of its expression and simultaneously revealed the nature of its promoter. This enabled investigation into the factors controlling these characteristics, and this fascinating work is discussed by Jacques Drouin, whose lab has led the way in this area (Drouin 2016). Access to POMC sequences across a wide variety of species has permitted …