SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.

GTF2IRD1 is one of the genes implicated in Williams-Beuren syndrome, a disease caused by haploinsufficiency of certain dosage-sensitive genes within a hemizygous microdeletion of chromosome 7. GTF2IRD1 is a prime candidate for some of the major features of the disease, presumably caused by abnormall...

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Autores principales:	Jocelyn Widagdo, Kylie M Taylor, Peter W Gunning, Edna C Hardeman, Stephen J Palmer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc747b992ae44ab4931d6407dc917a2f
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spelling	oai:doaj.org-article:cc747b992ae44ab4931d6407dc917a2f2021-11-18T08:09:19ZSUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.1932-620310.1371/journal.pone.0049283https://doaj.org/article/cc747b992ae44ab4931d6407dc917a2f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23145142/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203GTF2IRD1 is one of the genes implicated in Williams-Beuren syndrome, a disease caused by haploinsufficiency of certain dosage-sensitive genes within a hemizygous microdeletion of chromosome 7. GTF2IRD1 is a prime candidate for some of the major features of the disease, presumably caused by abnormally reduced abundance of this putative transcriptional repressor protein. GTF2IRD1 has been shown to interact with the E3 SUMO ligase PIASxβ, but the significance of this relationship is largely unexplored. Here, we demonstrate that GTF2IRD1 can be SUMOylated by the SUMO E2 ligase UBC9 and the level of SUMOylation is enhanced by PIASxβ. A major SUMOylation site was mapped to lysine 495 within a conserved SUMO consensus motif. SUMOylation of GTF2IRD1 alters the affinity of the protein for binding partners that contain SUMO-interacting motifs, including a novel family member of the HDAC repressor complex, ZMYM5, and PIASxβ itself. In addition, we show that GTF2IRD1 is targeted for ubiquitination and proteasomal degradation. Cross regulation by SUMOylation modulates this process, thus potentially regulating the level of GTF2IRD1 protein in the cell. These findings, concerning post-translational control over the activity and stability of GTF2IRD1, together with previous work showing how GTF2IRD1 directly regulates its own transcription levels suggest an evolutionary requirement for fine control over GTF2IRD1 activity in the cell.Jocelyn WidagdoKylie M TaylorPeter W GunningEdna C HardemanStephen J PalmerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49283 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jocelyn Widagdo Kylie M Taylor Peter W Gunning Edna C Hardeman Stephen J Palmer SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.
description	GTF2IRD1 is one of the genes implicated in Williams-Beuren syndrome, a disease caused by haploinsufficiency of certain dosage-sensitive genes within a hemizygous microdeletion of chromosome 7. GTF2IRD1 is a prime candidate for some of the major features of the disease, presumably caused by abnormally reduced abundance of this putative transcriptional repressor protein. GTF2IRD1 has been shown to interact with the E3 SUMO ligase PIASxβ, but the significance of this relationship is largely unexplored. Here, we demonstrate that GTF2IRD1 can be SUMOylated by the SUMO E2 ligase UBC9 and the level of SUMOylation is enhanced by PIASxβ. A major SUMOylation site was mapped to lysine 495 within a conserved SUMO consensus motif. SUMOylation of GTF2IRD1 alters the affinity of the protein for binding partners that contain SUMO-interacting motifs, including a novel family member of the HDAC repressor complex, ZMYM5, and PIASxβ itself. In addition, we show that GTF2IRD1 is targeted for ubiquitination and proteasomal degradation. Cross regulation by SUMOylation modulates this process, thus potentially regulating the level of GTF2IRD1 protein in the cell. These findings, concerning post-translational control over the activity and stability of GTF2IRD1, together with previous work showing how GTF2IRD1 directly regulates its own transcription levels suggest an evolutionary requirement for fine control over GTF2IRD1 activity in the cell.
format	article
author	Jocelyn Widagdo Kylie M Taylor Peter W Gunning Edna C Hardeman Stephen J Palmer
author_facet	Jocelyn Widagdo Kylie M Taylor Peter W Gunning Edna C Hardeman Stephen J Palmer
author_sort	Jocelyn Widagdo
title	SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.
title_short	SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.
title_full	SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.
title_fullStr	SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.
title_full_unstemmed	SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.
title_sort	sumoylation of gtf2ird1 regulates protein partner interactions and ubiquitin-mediated degradation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cc747b992ae44ab4931d6407dc917a2f
work_keys_str_mv	AT jocelynwidagdo sumoylationofgtf2ird1regulatesproteinpartnerinteractionsandubiquitinmediateddegradation AT kyliemtaylor sumoylationofgtf2ird1regulatesproteinpartnerinteractionsandubiquitinmediateddegradation AT peterwgunning sumoylationofgtf2ird1regulatesproteinpartnerinteractionsandubiquitinmediateddegradation AT ednachardeman sumoylationofgtf2ird1regulatesproteinpartnerinteractionsandubiquitinmediateddegradation AT stephenjpalmer sumoylationofgtf2ird1regulatesproteinpartnerinteractionsandubiquitinmediateddegradation
_version_	1718422135694688256

SUMOylation of GTF2IRD1 regulates protein partner interactions and ubiquitin-mediated degradation.

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