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.