The protein-protein interaction network of human Sirtuin family

TL;DR

This study maps the human Sirtuin protein interaction network, revealing its extensive connectivity, modular structure, and relevance to diseases like cancer and aging, providing insights into their biological functions.

Contribution

It constructs and analyzes the comprehensive Sirtuin-related human interactome, highlighting its scale-free, modular nature and its association with key biological processes.

Findings

Sirtuin network encompasses 25% of the human interactome

Network exhibits scale-free degree distribution

Identified subnetworks related to cancer, aging, and post-translational modifications

Abstract

Protein-protein interaction networks are useful for studying human diseases and to look for possible health care through a holistic approach. Networks are playing an increasing and important role in the understanding of physiological processes such as homeostasis, signaling, spatial and temporal organizations, and pathological conditions. In this article we show the complex system of interactions determined by human Sirtuins (Sirt) largely involved in many metabolic processes as well as in different diseases. The Sirtuin family consists of seven homologous Sirt-s having structurally similar cores but different terminal segments, being rather variable in length and/or intrinsically disordered. Many studies have determined their cellular location as well as biological functions although molecular mechanisms through which they act are actually little known. Therefore, the aim of this work was to define, explore and understand the Sirtuin-related human interactome. As a first step, we have integrated the experimentally determined protein-protein interactions of the Sirtuin-family as well as their first and second neighbors to a Sirtuin-related sub-interactome. Our data showed that the second-neighbor network of Sirtuins encompasses 25% of the entire human interactome, exhibits a scale-free degree distribution and interconnectedness among top degree nodes. Moreover, the Sirtuin sub interactome showed a modular structure around the core comprising mixed functions. Finally, we extracted from the Sirtuin sub-interactome subnets related to cancer, aging and post-translational modifications for information on key nodes and topological space of the subnets in Sirt family network.