RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity

Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of t...

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Autores principales:	Druker, J., Liberman, A.C., Antunica-Noguerol, M., Gerez, J., Paez-Pereda, M., Rein, T., Iñiguez-Lluhí, J.A., Holsboer, F., Arzta, E.
Formato:	JOUR
Materias:	glucocorticoid receptor nuclear receptor coactivator 2 small interfering RNA article controlled study female gene activity gene expression gene mutation gene silencing genetic transcription human human cell in vitro study priority journal protein interaction protein processing sumoylation Animals Arginine Carrier Proteins Cell Line Cercopithecus aethiops COS Cells Heat-Shock Response Mutation Nerve Tissue Proteins Protein Structure, Tertiary Rats Receptors, Glucocorticoid Sumoylation Transcription Factors Transcriptional Activation
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_02707306_v33_n11_p2116_Druker
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_02707306_v33_n11_p2116_Druker2023-10-03T15:14:51Z RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity Druker, J. Liberman, A.C. Antunica-Noguerol, M. Gerez, J. Paez-Pereda, M. Rein, T. Iñiguez-Lluhí, J.A. Holsboer, F. Arzta, E. glucocorticoid receptor nuclear receptor coactivator 2 small interfering RNA article controlled study female gene activity gene expression gene mutation gene silencing genetic transcription human human cell in vitro study priority journal protein interaction protein processing sumoylation Animals Arginine Carrier Proteins Cell Line Cercopithecus aethiops COS Cells Heat-Shock Response Mutation Nerve Tissue Proteins Protein Structure, Tertiary Rats Receptors, Glucocorticoid Sumoylation Transcription Factors Transcriptional Activation Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation.We nowdemonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulatesGRtranscriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating thatGRSUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-inducedGRSUMOylation. These results show that inhibitory and stimulatorySUMOsites are present in theGRand at higher SUMOylation levels the stimulatory one becomes dominant. © 2013, American Society for Microbiology. Fil:Druker, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Liberman, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gerez, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Paez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02707306_v33_n11_p2116_Druker
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	glucocorticoid receptor nuclear receptor coactivator 2 small interfering RNA article controlled study female gene activity gene expression gene mutation gene silencing genetic transcription human human cell in vitro study priority journal protein interaction protein processing sumoylation Animals Arginine Carrier Proteins Cell Line Cercopithecus aethiops COS Cells Heat-Shock Response Mutation Nerve Tissue Proteins Protein Structure, Tertiary Rats Receptors, Glucocorticoid Sumoylation Transcription Factors Transcriptional Activation
spellingShingle	glucocorticoid receptor nuclear receptor coactivator 2 small interfering RNA article controlled study female gene activity gene expression gene mutation gene silencing genetic transcription human human cell in vitro study priority journal protein interaction protein processing sumoylation Animals Arginine Carrier Proteins Cell Line Cercopithecus aethiops COS Cells Heat-Shock Response Mutation Nerve Tissue Proteins Protein Structure, Tertiary Rats Receptors, Glucocorticoid Sumoylation Transcription Factors Transcriptional Activation Druker, J. Liberman, A.C. Antunica-Noguerol, M. Gerez, J. Paez-Pereda, M. Rein, T. Iñiguez-Lluhí, J.A. Holsboer, F. Arzta, E. RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
topic_facet	glucocorticoid receptor nuclear receptor coactivator 2 small interfering RNA article controlled study female gene activity gene expression gene mutation gene silencing genetic transcription human human cell in vitro study priority journal protein interaction protein processing sumoylation Animals Arginine Carrier Proteins Cell Line Cercopithecus aethiops COS Cells Heat-Shock Response Mutation Nerve Tissue Proteins Protein Structure, Tertiary Rats Receptors, Glucocorticoid Sumoylation Transcription Factors Transcriptional Activation
description	Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation.We nowdemonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulatesGRtranscriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating thatGRSUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-inducedGRSUMOylation. These results show that inhibitory and stimulatorySUMOsites are present in theGRand at higher SUMOylation levels the stimulatory one becomes dominant. © 2013, American Society for Microbiology.
format	JOUR
author	Druker, J. Liberman, A.C. Antunica-Noguerol, M. Gerez, J. Paez-Pereda, M. Rein, T. Iñiguez-Lluhí, J.A. Holsboer, F. Arzta, E.
author_facet	Druker, J. Liberman, A.C. Antunica-Noguerol, M. Gerez, J. Paez-Pereda, M. Rein, T. Iñiguez-Lluhí, J.A. Holsboer, F. Arzta, E.
author_sort	Druker, J.
title	RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_short	RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_full	RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_fullStr	RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_full_unstemmed	RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_sort	rsume enhances glucocorticoid receptor sumoylation and transcriptional activity
url	http://hdl.handle.net/20.500.12110/paper_02707306_v33_n11_p2116_Druker
work_keys_str_mv	AT drukerj rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT libermanac rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT antunicanoguerolm rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT gerezj rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT paezperedam rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT reint rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT iniguezlluhija rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT holsboerf rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity AT arztae rsumeenhancesglucocorticoidreceptorsumoylationandtranscriptionalactivity
_version_	1807316487995654144

RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity

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