Acetylation and MAPK phosphorylation cooperate to regulate the degradation of active GATA-1.
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.
Hernandez-Hernandez
Angel
A
Section of Gene Function and Regulation, Institute of Cancer Research, London, UK.
Ray
Pampa
P
Litos
Gabi
G
Ciro
Marco
M
Ottolenghi
Sergio
S
Beug
Hartmut
H
Boyes
Joan
J
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
D050982:GATA1 Transcription Factor; D025801:Ubiquitin; D020928:Mitogen-Activated Protein Kinases