Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2005) 9 OC29

BES2005 Oral Communications Oral Communication 4: Steroids (8 abstracts)

Characterisation of a novel protein interacting with the glucocorticoid receptor

LM Rice 1 , CE Waters 2 , HJ Garside 1 , A White 1 & DW Ray 1


1Endocrine Sciences Research Group, University of Manchester, Manchester, UK; 2Centre for Vascular Biology and Medicine, King's College London, University of London, London, UK.


Glucocorticoids (Gcs) exert their pleiotropic effects through activation of the ubiquitously expressed glucocorticoid receptor (GR). The mechanism of transcriptional activation by the GR involves interaction with co-modulator proteins. Glucocorticoid sensitivity is mediated by the expression level of these co-modulator proteins and GR concentration. Therefore, the aim of this study was to identify additional GR interacting proteins that may influence glucocorticoid sensitivity by using a yeast two-hybrid genetic screen.

One of the cDNAs identified as interacting with the GR encoded a novel protein that showed an enhanced interaction with GR in the presence of antagonist, RU486. Database analysis identified 100% identity of this sequence with sequence on human chromosome 17. Bioinformatics analysis identified a 4-exon gene, with an open reading frame identical to the identified cDNA. This predicted a small protein of 121 amino acids, conserved in human, mouse and rat genomes. Northern blot analysis of a human multi-tissue filter identified a prominent transcript of 3kB with high-level expression in placenta, heart and muscle. Further bioinformatics analysis predicted a spliced transcript 3kB in length.

Using a GST pull down assay, this protein was found to interact constitutively with the full length GR with no additional effect of ligand binding. Transfection studies showed that the GR-interacting protein inhibited Gc transactivation of a simple reporter gene (MMTV) in human A549 cells. Immunocytochemistry revealed a mainly nuclear location of the protein when expressed with a cmyc-tag as expected of a transcriptional modulator.

We have identified a novel GR interacting protein that can modulate glucocorticoid sensitivity. We propose that this novel protein may play an important role in the mechanism of Gc-resistance in certain disease states and hence shows potential as a possible therapeutic target.

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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