The newly associated gene, called TBK1
(TANK-Binding Kinase 1), plays a key role at the intersection of two essential cellular pathways: inflammation (a reaction to injury or infection) and autophagy (a cellular process involved in the removal of damaged cellular components).
Abbreviations SOD1: Superoxide dismutase 1 ALS2: Alsin SETX: Senataxin SPG11: Spastic paraplegia 11 FUS: Fused in sarcoma RNA binding protein VAMP: Vesicle-associated membrane protein VAPB: Associated protein B and C ANG: Angiogenin TARDBP: TAR DNA-binding protein FIG4: FIG4 phosphoinositide 5-phosphatase OPTN: Optineurin ATXN2: Ataxin-2 C9ORF72: Chromosome 9 open reading frame 72 VEGF: Vascular endothelial growth factor IFN-[gamma]: Interferon gamma TNF-[alpha]: Tumor necrosis factor ILs: Interleukins IL-1[beta]: Interleukin 1 beta UBC: Ubiquitin C TBK1
: TANK-binding kinase 1 SQSTM1: Sequestosome 1 DCTN1: Dynactin subunit 1 IMPAS-1: Histocompatibility minor 13.
The presences of TLR4, MyD88, IRAK1, TRAF6, TAK1, JNK, MAPK, I[kappa]B[alpha], NF-[kappa]B, TRIF, TRAF3, TBK1
, IKKe, and IRF3 have all been confirmed by immunoblot analysis [2, 25].
MAVS and TRIF signal via the kinases IKK and TBK1
, resulting in translocation of the transcription factors NF-[kappa]B and IRF3 to the nucleus.
Mechanistically, upon the activation, an array of downstream protein including TRAF3 and TBK1
Zhu et al., "NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1
for degradation via the ubiquitin ligase DTX4," Nature Immunology, vol.
In the latter case, TRIF activates two IKK related proteins through TRAF3, inducible IKK (IKKi or IKK:), and TANK-binding kinase1 (TBK1
These genes can be grouped into several categories based on their protein function and their involvement in (i) protein homeostasis, such as optineurin , valosin-containing protein , ubiquilin 2 , and TBK1
; (ii) RNA metabolism and function such as TAR DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS) , C9orf72 [13,14], matrin 3 , and angiogenin ); (iii) cytoskeletal dynamics of motor axons such as dynactin subunit 1 , profilin 1 , and tubulin alpha-4 A chain ; (iv) mitochondrial function such as CHCHD10 ; and (v) regulation of inflammation such as TBK1
TRAF3, an E3 ligase like TRAF6, promotes TRAF6-independent  IRF3 phosphorylation by ubiquitination of TANK-binding kinase 1 (TBK1
) and formation of IKK[epsilon]/TBK1 complex.
Among them, NS2B/3 can inhibit the phosphorylation of serine 386 and nuclear transfer of IRF3, which result from the interaction between NS2B/3 protein enzyme and IKK[epsilon] , while the NS4A of DENV-1 inhibits RIG-I and TBK1
inducing IFN-0 .
After recruitment, TRIF interacts with TRAF6, which activates TRAF family member-associated NF-[kappa]B activator-binding kinase 1 (TBK1
) and IKK-[epsilon] for phosphorylation of IRFs.
Barber, "Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-[kappa]B activation through TBK1
," Journal of Virology, vol.