title: Acetylation and MAPK phosphorylation cooperate to regulate the degradation of active GATA-1.
abstract: Regulation of transcription requires mechanisms to both activate and terminate transcription factor activity. GATA-1 is a key haemopoietic transcription factor whose activity is increased by acetylation. We show here that acetylated GATA-1 is targeted for degradation via the ubiquitin/proteasome pathway. Acetylation positively signals ubiquitination, suggesting that activation by acetylation simultaneously marks GATA-1 for degradation. Promoter-specific MAPK phosphorylation then cooperates with acetylation to execute protein loss. The requirement for both modifications is novel and suggests a way by which degradation of the active protein can be specifically regulated in response to external phosphorylation-mediated signalling. As many transcription factors are activated by acetylation, we suggest that this might be a general mechanism to control transcription factor activity.
authors.affiliation: Section of Gene Function and Regulation, Institute of Cancer Research, London, UK.
authors.forename: Angel
authors.initials: A
authors.lastname: Hernandez-Hernandez
authors.forename: Pampa
authors.initials: P
authors.lastname: Ray
authors.forename: Gabi
authors.initials: G
authors.lastname: Litos
authors.forename: Marco
authors.initials: M
authors.lastname: Ciro
authors.forename: Sergio
authors.initials: S
authors.lastname: Ottolenghi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Beug
authors.forename: Joan
authors.initials: J
authors.lastname: Boyes
mesh_terms: D000107:Acetylation; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D050982:GATA1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D050982:GATA1 Transcription Factor; D025801:Ubiquitin; D020928:Mitogen-Activated Protein Kinases