P300 transcriptional repression is mediated by SUMO modification

D Girdwood; D Bumpass; OA Vaughan; A Thain; LA Anderson; AW Snowden; E Garcia-Wilson; ND Perkins; Ronald Thomas Hay

doi:10.1016/S1097-2765(03)00141-2

P300 transcriptional repression is mediated by SUMO modification

D Girdwood, D Bumpass, OA Vaughan, A Thain, LA Anderson, AW Snowden, E Garcia-Wilson, ND Perkins, Ronald Thomas Hay

School of Biology

Research output: Contribution to journal › Article › peer-review

Abstract

p300 and CREB binding protein can both activate and repress transcription. Here, we locate the CRD1 transcriptional repression domain between residues 1017 and 1029 of p300. This region contains two copies of the sequence psiKxE that are modified by the ubiquitin-like protein SUMO-1. Mutations that reduce SUMO modification increase p300-mediated transcriptional activity and expression of a SUMO-specific protease or catalytically inactive Ubc9 relieved repression, demonstrating that p300 repression was mediated by SUMO conjugation. SUMO-modified CRD1 domain bound HDAC6 in vitro, and p300 repression was relieved by histone deacetylase inhibition and siRNA-mediated ablation of HDAC6 expression. These results reveal a mechanism controlling p300 function and suggest that SUMO-dependent repression is mediated by recruitment of HDAC6.

Original language	English
Pages (from-to)	1043-1054
Number of pages	12
Journal	Molecular Cell
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/S1097-2765(03)00141-2
Publication status	Published - Apr 2003

Keywords

Creb-binding-protein
NF-kappa-B
Nuclear-bodies
E3 Ligase
Conjugating enzyme
Beta-catenin
PML
P53
Transactivation
UBIQUITIN

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10.1016/S1097-2765(03)00141-2

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@article{58b2239049b24113b64704b5790094b4,

title = "P300 transcriptional repression is mediated by SUMO modification",

abstract = "p300 and CREB binding protein can both activate and repress transcription. Here, we locate the CRD1 transcriptional repression domain between residues 1017 and 1029 of p300. This region contains two copies of the sequence psiKxE that are modified by the ubiquitin-like protein SUMO-1. Mutations that reduce SUMO modification increase p300-mediated transcriptional activity and expression of a SUMO-specific protease or catalytically inactive Ubc9 relieved repression, demonstrating that p300 repression was mediated by SUMO conjugation. SUMO-modified CRD1 domain bound HDAC6 in vitro, and p300 repression was relieved by histone deacetylase inhibition and siRNA-mediated ablation of HDAC6 expression. These results reveal a mechanism controlling p300 function and suggest that SUMO-dependent repression is mediated by recruitment of HDAC6.",

keywords = "Creb-binding-protein, NF-kappa-B, Nuclear-bodies, E3 Ligase, Conjugating enzyme, Beta-catenin, PML, P53, Transactivation, UBIQUITIN",

author = "D Girdwood and D Bumpass and OA Vaughan and A Thain and LA Anderson and AW Snowden and E Garcia-Wilson and ND Perkins and Hay, {Ronald Thomas}",

note = "This work was supported by the Medical Research Council, Cancer Research UK, Wellcome Trust, Biotechnology and Biological Sciences Research Council, and the University of St Andrews Development fund. N.D.P. is funded by a Royal Society University Fellowship.",

year = "2003",

month = apr,

doi = "10.1016/S1097-2765(03)00141-2",

language = "English",

volume = "11",

pages = "1043--1054",

journal = "Molecular Cell",

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publisher = "Cell Press",

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TY - JOUR

T1 - P300 transcriptional repression is mediated by SUMO modification

AU - Girdwood, D

AU - Bumpass, D

AU - Vaughan, OA

AU - Thain, A

AU - Anderson, LA

AU - Snowden, AW

AU - Garcia-Wilson, E

AU - Perkins, ND

AU - Hay, Ronald Thomas

N1 - This work was supported by the Medical Research Council, Cancer Research UK, Wellcome Trust, Biotechnology and Biological Sciences Research Council, and the University of St Andrews Development fund. N.D.P. is funded by a Royal Society University Fellowship.

PY - 2003/4

Y1 - 2003/4

N2 - p300 and CREB binding protein can both activate and repress transcription. Here, we locate the CRD1 transcriptional repression domain between residues 1017 and 1029 of p300. This region contains two copies of the sequence psiKxE that are modified by the ubiquitin-like protein SUMO-1. Mutations that reduce SUMO modification increase p300-mediated transcriptional activity and expression of a SUMO-specific protease or catalytically inactive Ubc9 relieved repression, demonstrating that p300 repression was mediated by SUMO conjugation. SUMO-modified CRD1 domain bound HDAC6 in vitro, and p300 repression was relieved by histone deacetylase inhibition and siRNA-mediated ablation of HDAC6 expression. These results reveal a mechanism controlling p300 function and suggest that SUMO-dependent repression is mediated by recruitment of HDAC6.

AB - p300 and CREB binding protein can both activate and repress transcription. Here, we locate the CRD1 transcriptional repression domain between residues 1017 and 1029 of p300. This region contains two copies of the sequence psiKxE that are modified by the ubiquitin-like protein SUMO-1. Mutations that reduce SUMO modification increase p300-mediated transcriptional activity and expression of a SUMO-specific protease or catalytically inactive Ubc9 relieved repression, demonstrating that p300 repression was mediated by SUMO conjugation. SUMO-modified CRD1 domain bound HDAC6 in vitro, and p300 repression was relieved by histone deacetylase inhibition and siRNA-mediated ablation of HDAC6 expression. These results reveal a mechanism controlling p300 function and suggest that SUMO-dependent repression is mediated by recruitment of HDAC6.

KW - Creb-binding-protein

KW - NF-kappa-B

KW - Nuclear-bodies

KW - E3 Ligase

KW - Conjugating enzyme

KW - Beta-catenin

KW - PML

KW - P53

KW - Transactivation

KW - UBIQUITIN

UR - http://www.sciencedirect.com/science/article/pii/S1097276503001412

U2 - 10.1016/S1097-2765(03)00141-2

DO - 10.1016/S1097-2765(03)00141-2

M3 - Article

SN - 1097-2765

VL - 11

SP - 1043

EP - 1054

JO - Molecular Cell

JF - Molecular Cell

IS - 4

ER -

P300 transcriptional repression is mediated by SUMO modification

Abstract

Keywords

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