title: Dynamic modification of the ETS transcription factor PEA3 by sumoylation and p300-mediated acetylation.
abstract: Transcription factor activity is often controlled through the dynamic use of post-translational modifications. Two such modifications are acetylation and sumoylation, which both occur on lysine residues, providing the opportunity for cross-talk at the molecular level. Here, we focussed on the ETS-domain transcription factor PEA3 and studied the potential interplay between these two modifications. We demonstrate that PEA3 is acetylated in a p300-dependent manner. ERK MAPK pathway signalling potentiates acetylation of PEA3, and enhances its trans-activation capacity. However, the major acetylation and sumoylation events take place on the same sites in PEA3 making simultaneous modification impossible. Indeed, manipulation of either the sumoylation or acetylation pathways causes reciprocal changes in PEA3 acetylation and sumoylation respectively. However, despite the mutually exclusive nature of these modifications, both contribute to the trans-activation capacity of PEA3, implying that a dynamic series of modification events occurs during the activation process.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Baoqiang
authors.initials: B
authors.lastname: Guo
authors.forename: Niki
authors.initials: N
authors.lastname: Panagiotaki
authors.forename: Stacey
authors.initials: S
authors.lastname: Warwood
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D058207:Sumoylation; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C065788:transcription factor PEA3