Inter-species functional interactome of nuclear steroid receptors (R1).

Abstract

Steroids exert their actions by binding to the glucocorticoid, mineralocorticoid, androgen, estrogen and progesterone classes of receptors. Despite an exponential increase in our knowledge of steroid receptors, their interactions with other molecules, subcellular location and functions still need further elucidation. To unravel the mechanism(s) of action of the steroid hormones, as well as the function of their cognate nuclear receptors, an interaction network was created (henceforth referred to as "R1 Interactome")- illustrating that robust interactions have been preserved in rodents, frog, zebra fish and drosophila. The generated interactome of the retrieved orthologs across species revealed: a. interactions among surface-cytosol-nuclear receptors, and/or orphan receptors and genes, and b. nuclear corepressor 1 (NCOR1) as a major "hub", through which most steroid receptors interact. These mechanisms (i) integrate social behavior and environmental stimuli with intrinsic cellular functions, (ii) provide an explanatory mechanism of the major Public Health problem of "non-ionizing" radiation impact, surpassing the existing conflict over the "thermal"/ "non- thermal" consequences of radiation, linking all the so far proposed mechanisms, and addressing all reported effects in humans, rodents and insects, and (iii) reveal biologically or clinically important pathways and/or regulatory networks.