scholarly journals Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor

2002 ◽  
Vol 367 (3) ◽  
pp. 907-911 ◽  
Author(s):  
Sha TIAN ◽  
Hetti POUKKA ◽  
Jorma J. PALVIMO ◽  
Olli A. JÄNNE
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Receptor Function ◽  
Dna Interactions ◽  
Mouse Mammary Tumour Virus ◽  
Cellular Targets ◽  
Attachment Sites ◽  
Protein Dna Interactions ◽  
Regulate Protein ◽  
Virus Promoter

Small ubiquitin-related modifier-1 (SUMO-1) is covalently attached to many cellular targets to regulate protein—protein and protein—DNA interactions, as well as localization and stability of the target protein. The SUMO-1-conjugating E2 enzyme Ubc9 is known to interact with the glucocorticoid receptor (GR), a ligand-dependent transcription factor. In the present study, we show that GR is post-translationally modified by SUMO-1 (sumoylated) in a ligand-enhanced fashion. We identify experimentally three consensus SUMO attachment sites, two in the N-terminal transactivation region and one in the ligand-binding domain of GR. The two N-terminal sites are the major acceptor sites for SUMO-1 attachment. Mutation of these sites enhances transcriptional activity of GR on minimal promoters, but has no clear effect on the more complex mouse mammary tumour virus promoter. Thus SUMO-1 modification of GR influences receptor function in a promoter context-dependent fashion.

scholarly journals Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

2018 ◽  
Author(s):  
Ramasubramanian Sundaramoorthy ◽  
Amanda L. Hughes ◽  
Hassane El-Mkami ◽  
David Norman ◽  
Tom Owen-Hughes
Keyword(s):  
Histone H3 ◽  
Bound State ◽  
Chromatin Remodelling ◽  
Dna Interactions ◽  
Histone Octamer ◽  
Nucleosome Structure ◽  
Protein Dna Interactions ◽  
Dna Strands ◽  
Regulate Protein ◽  
Related Proteins

AbstractATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the yeast Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

scholarly journals Mitogen-activated and cyclin-dependent protein kinases selectively and differentially modulate transcriptional enhancement by the glucocorticoid receptor.

1997 ◽  
Vol 17 (7) ◽  
pp. 3947-3954 ◽  
Author(s):  
M D Krstic ◽  
I Rogatsky ◽  
K R Yamamoto ◽  
M J Garabedian
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Mitogen Activated Protein Kinase ◽  
Cyclin Dependent Kinase ◽  
Receptor Function ◽  
Yeast Strains ◽  
Mitogen Activated Protein ◽  
Dependent Protein

Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232. Mutations in these kinases have opposite effects on receptor transcriptional activity in vivo. Receptor-dependent transcriptional enhancement is reduced in yeast strains deficient in the catalytic (p34CDC28) or certain regulatory (cyclin) subunits of CDK complexes and is increased in a strain devoid of the mammalian MAPK homologs FUS3 and KSS1. These findings indicate that the glucocorticoid receptor is a target for multiple kinases in vivo, which either positively or negatively regulate receptor transcriptional enhancement. The control of receptor transcriptional activity via phosphorylation provides an increased array of regulatory inputs that, in addition to steroid hormones, can influence receptor function.

scholarly journals Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ramasubramanian Sundaramoorthy ◽  
Amanda L Hughes ◽  
Hassane El-Mkami ◽  
David G Norman ◽  
Helder Ferreira ◽  
...  
Keyword(s):  
Histone H3 ◽  
Bound State ◽  
Chromatin Remodelling ◽  
Dna Interactions ◽  
Histone Octamer ◽  
Nucleosome Structure ◽  
Protein Dna Interactions ◽  
Dna Strands ◽  
Regulate Protein ◽  
Related Proteins

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein–DNA interactions. Here, we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

scholarly journals Glucocorticoid Receptor–DNA Interactions: Binding Energetics Are the Primary Determinant of Sequence-Specific Transcriptional Activity

2012 ◽  
Vol 422 (1) ◽  
pp. 18-32 ◽  
Author(s):  
David L. Bain ◽  
Qin Yang ◽  
Keith D. Connaghan ◽  
James P. Robblee ◽  
Michael T. Miura ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Dna Interactions ◽  
Binding Energetics ◽  
Primary Determinant

Modulating glucocorticoid receptor function in breast and prostate cancer

2018 ◽  
Author(s):  
E. Tonsing-Carter ◽  
T. Long ◽  
D.C. West ◽  
R. Harkless ◽  
D.N. Dolcen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glucocorticoid Receptor ◽  
Receptor Function ◽  
Breast And Prostate Cancer
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