SFEBES2009 Poster Presentations Steroids (36 abstracts)
Cofactors and modify Cofactors and modifications of the glucocorticoid receptor
L Davies , A Gkourtza , C Symeou , J Lynch , S Taylor , C Demonacos & M Krstic-Demonacos
The University of Manchester, Manchester, UK.
The glucocorticoid receptor (GR) is a member of the nuclear hormone receptor superfamily that acts as a hormone responsive transcription factor. GR function is controlled by hormone binding, post-translational modifications and through interaction with cofactors. Here, we report that JNK dependent phosphorylation of GR affects its sumoylation. JNK activation by UV radiation that targets GR for phosphorylation at serine 246 (S246) facilitated subsequent GR sumoylation at lysines 297 and 313. Furthermore, we detected that sumoylation of GR modulates its phosphorylation status because the GR derivative K297R/K313R that is sumoylation- deficient shows altered pattern of S246 phosphorylation thus creating a regulatory feedback loop.
Another level of control of the GR function by phosphorylation is its protein stability. Our evidence suggests that stability of the GR is altered by JNK activation in both the absence and presence of hormone and that other cofactors also play a role in this process. Finally, endogenous GR transcriptional activity was affected in a target gene specific manner by JNK and SUMO pathway activation. We conclude that interplay of signalling pathways and cofactors affect GR protein stability and target gene selectivity, thereby modulating the hormonal response of cells exposed to stress.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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