Nuclear receptor coregulators

A Large Number of Nuclear Receptor Coregulators Also Participate in Regulating Transcription... 

Hermanson O, Glass CK, Rosenfeld MG Nuclear receptor coregulators multiple modes of receptor modification. Trends Endocrinol Metab 2002 13 55. 

McKenna NJ, Lanz RB, O Malley BW (1999) Nuclear receptor coregulators cellular and molecular biology. Endocr Rev 20 321... 

NUCLEAR RECEPTOR COREGULATORS AND EPIGENETIC REGULATION OF GENE TRANSCRIPTION... 

Hermanson, O., C. K. Glass, and M. G. Rosenfeld. 2002. Nuclear receptor coregulators multiple modes of modification. Trends Endocrinol. Metab. 13 55-60. 

Lonard, D. M., and O Malley B, W. Nuclear receptor coregulators judges, juries, and executioners of cellular regulation. Mol Cell 27 (2007) 691-700. 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

Chromatin remodeling, transcription factor modification by various enzyme activities, and the communication between the nuclear receptors and the basal transcription apparatus are accomplished by protein-protein interactions with one or more of a class of coregulator molecules. The number of these coregulator molecules now exceeds 100, not counting species variations and splice variants. The first of these to be described was the CREB-binding protein, CBP. CBP, through an amino terminal domain, binds to phosphorylated serine 137 of CREB and mediates transactivation in response to cAMP. It thus is described as a coactivator. CBP and... 

Another large family of coregulator proteins remodel chromatin, modify other transcription factots, and bridge the nuclear receptors to the basal ttanscription apparatus. 

McKenna, N. and O Malley, B. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108 465-474,2002. 

Glass, C. and Rosenfeld, M. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14 121-141,2000. 

Rosenfeld MG, Glass CK (2001) Coregulator codes of transcriptional regulation by nuclear receptors. J Biol Chem 276 36865-36868... 

The interaction of glucocorticoid receptors with GREs or other transcription factors is facilitated or inhibited by several families of proteins called steroid receptor coregulators, divided into coactivators and corepressors. The coregulators do this by serving as bridges between the receptors and other nuclear proteins and by expressing enzymatic activities such as histone acetylase or deacetylase, which alter the... 

Ruan XZ, Varghese Z, Powis SH, Moorhead JF (2005) Nuclear receptors and their coregulators in kidney. Kidney Int, 68(6) 2444-2461. 

However, some receptors are constitutively expressed in the nucleus and this type of receptor would not be amenable to a nuclear translocation assay. The activities of nuclear receptors may be dependent upon complex interactions with a number of coregulatory proteins, commonly known as coactivators or corepressors, and modifications by post-translational means. Cell type-specific expression levels of receptors and coregulators may contribute to some, but not all, of the molecular bases for gene and functional selectivity of receptor activity. Therefore selecting a cell line that expresses both the target receptor and the necessary cofactors may be required to design an appropriate assay. 

Nettles KW, Greene GL. Ligand control of coregulator recruitment to nuclear receptors. Annu. Rev. Physiol. 2005 67 309-333. Ingraham HA, Redinbo MR. Orphan nuclear receptors adopted by crystallography. Curr. Opin. Struct. Biol. 2005 15 708-715. DeLano WL. MacPyMOL a PyMOL-based Molecular Graphics Application for MacOS X. 2007. DeLano Scientific LLC, Palo Alto, CA. 

Robyr D, Wolffe AP, Wahli W. Nuclear hormone receptor coregulators in action diversity for shared tasks. Mol. Endocrinol. 2000 14 329-347. 

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