Liquid phase separation of NEMO induced by polyubiquitin chains activates NF-κB.
Mol Cell
; 82(13): 2415-2426.e5, 2022 07 07.
Article
in En
| MEDLINE
| ID: mdl-35477005
ABSTRACT
The NF-κB essential modulator (NEMO) is a regulatory subunit of the IκB kinase (IKK) complex that phosphorylates the NF-κB inhibitors IκBs. NEMO mediates IKK activation by binding to polyubiquitin chains (polyUb). Here, we show that Lys63(K63)-linked or linear polyUb binding to NEMO robustly induced the formation of liquid-like droplets in which IKK was activated. This liquid phase separation of NEMO was driven by multivalent interactions between NEMO and polyUb. Both the NEMO ubiquitin-binding (NUB) domain and the zinc-finger (ZF) domain of NEMO mediated binding to polyUb and contributed to NEMO phase separation and IKK activation in cells. Moreover, NEMO mutations associated with human immunodeficiency impaired its phase separation. These results demonstrate that polyUb activates IKK and NF-κB signaling by promoting the phase separation of NEMO.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
NF-kappa B
/
Polyubiquitin
Limits:
Humans
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Type:
Article
Affiliation country:
United States