Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates

Wenli Yang, William G. Robichaux, Fang C. Mei, Wei Lin, Li Li, Sheng Pan, Mark A. White, Yuan Chen, Xiaodong Cheng

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Protein SUMOylation plays an essential role in maintaining cellular homeostasis when cells are under stress. However, precisely how SUMOylation is regulated, and a molecular mechanism linking cellular stress to SUMOylation, remains elusive. Here, we report that cAMP, a major stress-response second messenger, acts through Epac1 as a regulator of cellular SUMOylation. The Epac1-associated proteome is highly enriched with components of the SUMOylation pathway. Activation of Epac1 by intracellular cAMP triggers phase separation and the formation of nuclear condensates containing Epac1 and general components of the SUMOylation machinery to promote cellular SUMOylation. Furthermore, genetic knockout of Epac1 obliterates oxidized low-density lipoprotein–induced cellular SUMOylation in macrophages, leading to suppression of foam cell formation. These results provide a direct nexus connecting two major cellular stress responses to define a molecular mechanism in which cAMP regulates the dynamics of cellular condensates to modulate protein SUMOylation.

Original languageEnglish (US)
Article numbereabm2960
JournalScience Advances
Volume8
Issue number16
DOIs
StatePublished - Apr 2022

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates'. Together they form a unique fingerprint.

Cite this