  Cellular networks undergo rearrangements during stress and diseases. In
un-stressed state the yeast protein-protein interaction network (interactome)
is highly compact, and the centrally organized modules have a large overlap.
During stress several original modules became more separated, and a number of
novel modules also appear. A few basic functions, such as the proteasome
preserve their central position. However, several functions with high energy
demand, such the cell-cycle regulation loose their original centrality during
stress. A number of key stress-dependent protein complexes, such as the
disaggregation-specific chaperone, Hsp104, gain centrality in the stressed
yeast interactome. Molecular chaperones, heat shock, or stress proteins form
complex interaction networks (the chaperome) with each other and their
partners. Here we show that the human chaperome recovers the segregation of
protein synthesis-coupled and stress-related chaperones observed in yeast
recently. Examination of yeast and human interactomes shows that (1) chaperones
are inter-modular integrators of protein-protein interaction networks, which
(2) often bridge hubs and (3) are favorite candidates for extensive
phosphorylation. Moreover, chaperones (4) become more central in the
organization of the isolated modules of the stressed yeast protein-protein
interaction network, which highlights their importance in the de-coupling and
re-coupling of network modules during and after stress. Chaperone-mediated
evolvability of cellular networks may play a key role in cellular adaptation
during stress and various polygenic and chronic diseases, such as cancer,
diabetes or neurodegeneration.
