title: Acetylation and nuclear receptor action.
abstract: Acetylation is an essential post-translational modification featuring an acetyl group that is covalently conjugated to a protein substrate. Histone acetylation was first proposed nearly half a century ago by Dr. Vincent Allfrey. Subsequent studies have shown that the acetylated core histones are often associated with transcriptionally active chromatin. Acetylation at lysine residues of histone tails neutralizes the positive charge, which decreases their binding ability to DNA and increases the accessibility of transcription factors and coactivators to the chromatin template. In addition to histones, a number of non-histone substrates are acetylated. Acetylation of non-histone proteins governs biological processes, such as cellular proliferation and survival, transcriptional activity, and intracellular trafficking. We demonstrated that acetylation of transcription factors can regulate cellular growth. Furthermore, we showed that nuclear receptors (NRs) are acetylated at a phylogenetically conserved motif. Since our initial observations with the estrogen and androgen receptors, more than a dozen NRs have been shown to function as substrates for acetyltransferases with diverse functional consequences. This review focuses on the acetylation of NRs and the effect of acetylation on NR function. We discuss the potential role of acetylation in disease initiation and progression with an emphasis on tumorigenesis.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Tian
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Popov
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010802:Phylogeny; D011499:Protein Processing, Post-Translational; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D008024:Ligands; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D054339:Steroidogenic Factor 1; D051548:Histone Acetyltransferases