An Acetylation-Primed SUMOylation Switch Controls RORβ Stability through a p300-SIRT1 Regulatory Axis.

Authors

Patrick Griffin, Timothy O'Leary, Denis Shutin, Nadeska Montalvan, Nereida Abad-Yang, Vuong Dang, Dean Edwards, Mi Ra Chang

Published in

Research square. Jul 23, 2026. Epub Jul 23, 2026.

Abstract

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. Graphical Abstract.

PMID:
42539049
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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