Tuning NF-κB activity: a touch of COMMD proteins.
NF-κB is an important regulator of immunity and inflammation, and its activation pathway has been studied extensively. The mechanisms that downregulate the activity of NF-κB have also received a lot of attention, particularly since its activity needs to be terminated to prevent chronic inflammation and subsequent tissue damage. The COMMD family has been identified as a new group of proteins involved in NF-κB termination. All ten COMMD members share the structurally conserved carboxy-terminal motif, the COMM domain, and are ubiquitously expressed. They seem to play distinct and non-redundant roles in various physiological processes, including NF-κB signaling. In this review, we describe the mechanisms and proteins involved in the termination of canonical NF-κB signaling, with a specific focus on the role of the COMMD family in the down-modulation of NF-κB.
University of Groningen, University Medical Center Groningen, Molecular Genetics, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands.
Paulina
P
Bartuzi
Marten H
MH
Hofker
Bart
B
van de Sluis
D048868:Adaptor Proteins, Signal Transducing / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D016328:NF-kappa B
CFTR; COMMD; COMMD family; CRL; CRM1; CYLD; Cullin RING ligase; DUB; ENaC; HDAC; HIF; IKK; IL-1; IL-1R; Inflammation; IκB; IκB kinase; LPS; NES; NF-κB; NLS; PDLIM2; PDZ and LIM domain containing protein 2; PIAS; PML; REL homology domain; RHD; RING box protein; RIP1; Rbx; SNP; SOD1; Scaffold; TAD; TAK; TLR4; TNF; TNF-receptor associated factor; TNFAIP3; TNFα-induced protein 3; TRAF; Termination; X-linked inhibitor of apoptosis; XIAP; chromosome region maintenance 1/exportin 1; copper metabolism gene MURR1 domain-containing protein; cylindromatosis; cystic fibrosis transmembrane conductance regulator; deubiquitinating enzyme; epithelial sodium channel; histone deacetylase; hypoxia inducible factor; inhibitor of κB; interleukin-1; interleukin-1 receptor; lipopolysaccharide; nuclear export signal; nuclear factor κB; nuclear localization signal; promyelocytic leukemia protein; protein inhibitor of activated STAT; receptor-interacting protein 1; sCLU; secretory clusterin; single nucleotide polymorphism; superoxide dismutase 1; toll-like receptor 4; transactivation domain; transforming growth factor β-activated kinase; tumor necrosis factor