2021年8月19日 · We found that CYLD loses its inactivating phosphorylation mark faster in TBK1 null hTERTs than WT (Figure 3 D). We also found that complementation with WT TBK1 completely rescued pCYLD stability, but complementation with G159A, the kinase-dead allele from the patient who developed HSE without baseline autoinflammation, did so only partially ...

2020年2月5日 · ATLL cells overexpressing a kinase-inactive TBK1 (TBK1-K38A) demonstrate lower CYLD phosphorylation and subsequently reduced proliferation. IKK blockade reactivates CYLD, as evidenced by...

2008年7月18日 · The observations that CYLD can deubiquitinate TBK1 and inhibit the IRF3 response induced by TBK1 expression suggest that ubiquitination is also crucial for TBK1 function; however, it is unclear at present how attachment or removal of ubiquitin regulates the enzymatic activity of TBK1.

2011年9月26日 · Here we report that CYLD, a deubiquitinase that specifically digests lysine 63-linked ubiquitin chains, is required for antiviral host defense. Loss of CYLD renders mice considerably more...

2024年12月23日 · We show that TBK1 activation tightly regulates CYLD activity and RIPK1 activation upon CXCL4 and TLR8 costimulation while CYLD and RIPK1 are regulated by Caspase-8-mediated cleavage in either...

Our initial data indicated that CYLD is directly phosphorylated by the noncanonical IκB kinases (IKKs) IKKε and TANK Binding Kinase 1 (TBK1) at Ser418 upon TCR stimulation. Treatment with MRT67307, a small compound inhibitor for IKKε and TBK1, inhibited TCR-induced CYLD phosphorylation.

2021年8月19日 · TANK binding kinase 1 (TBK1) regulates IFN-I, NF-κB, and TNF-induced RIPK1-dependent cell death (RCD). In mice, biallelic loss of TBK1 is embryonically lethal. We discovered four humans, ages 32, 26, 7, and 8 from three unrelated consanguineous families with homozygous loss-of-function mutations in …

2022年9月1日 · We demonstrated that macrophage TXNIP deficiency controlled STING-mediated TBK1 function and alleviated IR-induced hepatocellular injury by regulating the cylindromatosis (CYLD)–NADPH oxidase 4 (NOX4) axis.

2021年8月6日 · TANK binding kinase 1 (TBK1) regulates IFN-I, NF-κB, and TNF-induced RIPK1-dependent cell death (RCD). In mice, biallelic loss of TBK1 is embryonically lethal. We discovered four humans, ages 32, 26, 7, and 8 from three unrelated consanguineous families with homozygous loss-of-function mutations in TBK1.

2008年7月4日 · CYLD deficiency causes constitutive activation of IKKepsilon/TBK1, which is associated with hyper-induction of IFNs in virus-infected cells. We further show that CYLD targets a cytoplasmic RNA sensor, RIG-I, and inhibits the …