Advances in post-translational modifications of proteins and aging

This volume contains 56 contributions presented at the 1st International Symposium on Post-Translational Modifications of Proteins and Ageing, held on the Island of Ischia (Naples, Italy) from May 11 to 15, 1987, under the auspices of the University of Naples and the Italian Society of Biochemistry. The primary aim of this interdisciplinary meeting was to promote a productive exchange among scientists from different cultural areas, and to give them the opportunity to discuss problems of common interest approached from different scientific standpoints. Although a large number of studies has led to a definition of the chemical mechanisms and of the main enzymological aspects of several post-translational modifications of proteins, we are still far away from a complete elucidation of the functional significance of such processes. As a matter of fact, it seems reasonable that the presently available experimental approaches and models employed to investigate the biological roles are still inadequate. The search for suitable model systems was a matter of discussion during the meeting, and will be a major challenge in the future. The most frequently employed approaches to this problem thus far have been in vitro, but several proteins reported to be excellent in vitro substrates failed to show any activity when assayed in in vivo models. The problem of substrate specificity has also been a much-discussed issue; the specificity determinants of this class of reactions have been extensively investigated in recent years, and in some instances the enzyme-substrate recognition sites have been elucidated. In many cases, primary sequence of the site of modification, as well as secondary and tertiary structures of substrate proteins, are all critical. Furthermore, substrate flexibility and site accessibility within the pertinent structural domains have also been proposed as relevant factors. Additional specificity determinants are the compartmentalization of many enzymes specificity determinants are the compartmentalization of many enzymes involved in the processing, as well as the dynamics of the sequence of various modifications often operative in the same protein. The first section of the book in concerned with general aspects of "Transglutaminase-Mediated Reactions" and their possible functional roles in the ageing of specific tissues. The second group of contributions in the ageing of specific tissues. The second group of contributions in the deals with "Protein Methylation"; significant attention has been directed to the methylesterification of proteins at the level of altered aspartyl residues, and to the role of this reaction in the processing of "aged" proteins. The chemical aspects and the complex regulatory functions of "Protein Prhoshorylation" are discussed in the third section, with special emphasis on the regulation of cell growth and transformation mediated by protein-tyrosline kinases. Additional post-translational modifications, such as ADP-ribosylation, protein glycosylation, and histone acetylation, comprise the last issue treated in this volume. We will consider our effects worthwhile if these Proceedings inform the readers, indicating new paths and stimulating novel approaches.