The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms

In this review, we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. In the beginning, we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section, the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteomes. Three sections are dedicated to the description of glycation and enzymatic glycosylation. Citrullination and N- and C-terminal post-translational modifications (PTMs) and miscellaneous other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed throughout the sections of the manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Automated summary

In this review, the main post-translational modifications leading to multiple proteoforms in the human salivary proteome are extensively described, along with their potential role. The majority of the data reported in this review were obtained through over twenty-five years of research on human saliva, primarily using a top-down strategy. Various proteolytic cleavage products, salivary protein families, phospho-proteome, sulfo-proteomes, glycation, enzymatic glycosylation, citrullination, N- and C-terminal post-translational modifications, and miscellaneous other modifications are discussed in different sections of the manuscript. Furthermore, the impact and relevance of these findings in the development of new diagnostic biomarkers for clinical practice are emphasized.