  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.
