Hormones were previously known to induce kinase signaling cascades from the cell surface to the nucleus. Nuclear receptors (NR) coordinate diverse biological phenotypes altering cellular metabolism, differentiation and cellular proliferation. The genes that regulate cell-cycle progression participate as targets of NR signaling and coordinate many of these responses. These cyclins and CDKs in turn feed back to modify NR activity. Proteins governing nuclear receptor (estrogen receptor a (ERa), androgen receptor (AR), TR, GR) function can be modified by acetylation. Such proteins include the co-activator (SRC1), co-integrator (p300, p/CAF), HSP-90, histones and HDACs. Phosphorylation, acetylation and ubiquitination occur within transcription factors as a form of intra-transcription factor signaling (signaling cascades within transcription factors; SCITS). The modification of nuclear receptors by acetylation determines gene expression specificity and is a key determining factor of cellular growth in hormone-responsive cells.
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