IndraLab

"USP15 inhibits the NF-κB pathway by removing K48-Ub from IκBα and consequently prevent degradation it."

"Three human DUBs, CYLD, A20 and DUBA, have been shown to negatively regulate the innate immune response by removing K63-based chains [55], [56], and USP15 inhibits the NFκB pathway by removing K48-Ub from IκBα, preventing its degradation [57]."

"Three human DUBs, CYLD, A20 and DUBA, have been shown to negatively regulate the innate immune response by removing K63-based chains [55, 56] , and USP15 inhibits the NFkB pathway by removing K48-Ub from IkBa, preventing its degradation [57] ."

"The NF‐kB signalling pathway plays critical role in regulation of innate and adaptive immunity, inflammation, apoptosis, cancer and tumour development. xref NF‐kB is a transcription factor, consists of five related proteins, p105/p50 (NF‐κB1) and p100/p52 (NF‐κB2), p65 (RelA), RelB and c‐Rel (Rel), which in resting state remain in the cytoplasm as dimers associated with the IκB inhibitor. xref There are eight IκB proteins, IκBα, IκBβ, IκBε, IκBζ, BCL‐3, IκBns and the precursor proteins NF‐κB2 and NF‐κB1, which are characterized by the presence of six to seven ankyrin repeat motifs (ANK) which have binding ability to NF‐κB dimers. xref , xref Therefore, in unstimulated cells, NF‐κB dimers bind to IκB inhibitor proteins in the cytoplasm because all NF‐κB proteins are characterized by the presence of a highly conserved Rel homology domain (RHD) in their N‐terminus, which contains a nuclear localization signal (NLS) and is responsible interaction with IκBs. xref Upon stimulation, IκB is phosphorylated in serine residues by the IκB kinase (IKK) complex, which consists of two catalytic subunits, IKKα (IKK1 or CHUK) and IKKβ (IKK2) and an NF‐κB essential modifier (NEMO, also known as IKKγ, IKKAP1 or Fip‐3). xref , xref Phosphorylated IκB creates a destruction motif recognized by the ubiquitin ligase complex and degraded by 26S proteasome, then NF‐κB complexes translocate to the nucleus and regulates the expression of its target genes. xref , xref Ubiquitination plays a crucial role in control of NF‐κB pathway as a major regulator of the immune response. xref USP15 inhibits the NF‐κB pathway by removing K48‐Ub from IκBα and consequently prevent degradation it."