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Updated: Aug 5, 2026

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
Published on: January 29, 2018
An Acetylation-Primed SUMOylation Switch Controls RORβ Stability through a p300-SIRT1 Regulatory Axis
Patrick Griffin1, Timothy O'Leary1, Denis Shutin1
1The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology.
None:
Retinoic acid receptor-related orphan receptor beta (RORβ) is a transcription factor expressed in the central nervous system, retina, and bone that regulates circadian rhythms, retinal neurogenesis, and inflammatory signaling. Despite these critical functions, the mechanisms governing RORβ stability remain poorly understood. Here, we identify a post-translational regulatory axis in which the lysine acetyltransferase p300 and the NAD+-dependent deacetylase SIRT1 control RORβ stability and transcriptional activity. p300-mediated acetylation increases RORβ abundance, while SIRT1 modulates turnover through both catalytic and non-catalytic scaffolding mechanisms. K176 acetylation in the hinge primes UBC9/PIAS1-mediated SUMOylation at nearby K179, marking RORβ for proteasomal degradation and reducing transcriptional output, providing a mechanistic framework for targeting RORβ in neurological and retinal disorders, and bone homeostasis.
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