IndraLab

Statements


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sparser
"Our results suggest a mechanism by which A20 inhibits IKK without deubiquitination or impairment of ubiquitination enzymes."

sparser
"The rates for IKK inactivation by A20 significantly affect the termination of initial NF-κB activity as well as the second phase of activity."

sparser
"Indeed, we present multiple lines of evidence that A20 inhibits IKK through a non-catalytic mechanism."

sparser
"It gathers recovery (via k 3 ) and dynamical properties (via k 9 ), as well as the A20 dependent inactivation (via k 4 ) of the kinase IKK."

sparser
"It has been found that A20 inhibits the IKK complex by non-catalytic functions, mediated by recruitment of A20 to the C-terminal domain of IKKα [31,32] ."

eidos
"( a ) In the TNF-induced NF-kappaB pathway , A20 can impair IKK complex activation , thus opposing the activation of NF-kappaB ."
| PMC

sparser
"Our analysis suggests that direct A20 inactivation of IKK contributes more to later regulation than feedback inhibition of IKK activation, although more detailed models are likely to provide better insight into the complex regulatory role of A20."

sparser
""The newly synthesizedI κ B α again inhibitsNF- κ B, while A20 inhibits IKK by catalysing its transformation into another inactive form, in which it is no longer capable ofphosphorylating I κ B α .""

sparser
"In this sense, our observation is similar to the previously reported noncatalytic mechanisms of IKK inhibition by A20 in the canonical pathway xref xref xref ."

eidos
"In short , all four models share a feedback inhibition of IKK activity by A20 but differ in the specifics of their A20 feedback implementations ."

eidos
"As a tumor suppressor , A20 directly inhibits IKK activation and HL cell survival via its C-terminal linear-ubiquitin binding ZF7 ."

sparser
"Recently, Skaug et al. reported a direct non-catalytic mechanism of IKK inhibition by A20 showing that overexpressed A20 impaired IKK activation without reducing RIP1 ubiquitination xref ."

eidos
"The three upstream modules comprise the three distinct mechanisms of IKK inhibition by A20 that Lipniacki et al. ( 2004 ) , Ashall et al. ( 2009 ) , and Murakawa et al. ( 2015 ) have proposed ."

sparser
"These include the deubiquitination enzymes CYLD and A20 that inhibit IKK, and the ubiquitin binding proteins NEMO and TAB2 which are the regulatory subunits of IKK and TAK1 kinase complexes, respectively."

sparser
"A second mechanism of IKK inhibition by A20 is mediated through its C-terminal zinc finger domains, which function as an E3 to promote K48-linked polyubiquitination of RIP1 and target it for degradation by the proteasome xref ."

sparser
"The newly synthesized IkappaBalpha leads NF-kappaB out of the nucleus and sequesters it in the cytoplasm, while A20 inhibits IKK converting IKKa into the inactive form (IKKi), a form different from IKKn, no longer capable of phosphorylating IkappaBalpha."

eidos
"IkappaBs ( NFKBIA [ IkappaBalpha ] , IKBKB [ IkappaBbeta ] , and IKBKE [ IkappaBepsilon ] ) and TNFAIP3 ( A20 ) are target genes of NF-kappaB ; when NF-kappaB is activated , IkappaBs are released from the DNA binding domain of NF-kappaB , and A20 suppresses IKK activation [ 144-146 ] ."

sparser
"However, direct evidence of IKK inhibition by A20 is lacking, and the inhibitory mechanism remains poorly understood."

sparser
"The newly synthesized I κ B α leads NF- κ B out of the nucleus and sequesters it in the cytoplasm ( Fig. 1 B ), while A20 inhibits IKK by converting IKKa into the inactive form IKKi ( Fig. 1 C ), a fo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Our results suggest a non-catalytic mechanism of IKK inhibition by A20 and a means by which polyubiquitin chains can specify a signaling outcome."

sparser
"These results provide direct evidence that A20 inhibits IKK by preventing the phosphorylation of IKK by TAK1."

reach
"In addition to TNFAIP3 modulating ubiquitin others have found that TNFAIP3 can also inhibit IKK complex activity through a mechanism that is independent of ubiquitin."

eidos
"TNF-induced expression of IkappaB attenuates NFkappaB , whereas A20 inhibits IKK and RIPK3 ."

sparser
"We found evidence that A20 can inhibit IKK through a mechanism that cannot be accounted for by reducing the interaction of polyubiquitin chains with NEMO."

sparser
"The newly synthesized I κ B α again inhibits NF- κ B, while A20 inhibits IKK by catalyzing its transformation into another inactive form in which it is no longer capable of phosphorylating I κ B α ."

sparser
"Our results therefore suggest a direct, non-catalytic mechanism of IKK inhibition by A20 and demonstrate that polyubiquitin chains can induce specific binding among proteins to which ubiquitin is not covalently attached."

sparser
"As a tool to dissect the mechanism of IKK inhibition by A20, we stably overexpressed Flag-A20 in a HEK293 cell line that expresses IL-1R. In this cell line, IKK activation by TNFα was almost completely abolished, as evidenced by the lack of IκBα degradation and the failure of immunoprecipitated IKK complex to phosphorylate IκBα ( xref )."

sparser
"The model simulations ( xref ) confirmed the experimental findings that RC3H1 reduces A20 mRNA and subsequently A20 protein expression, and, due to the attenuated IKK inhibition by A20, leads to an increased IKK activity."

sparser
"The three upstream modules comprise the three distinct mechanisms of IKK inhibition by A20 that xref , xref , and xref have proposed."

sparser
"A20 Inhibits IKK Downstream of TRAF6 Through a Non-Catalytic Mechanism."

sparser
"To further dissect the mechanism of IKK inhibition by A20, we tested whether purified A20 protein could inhibit IKK activation by TRAF6 in a cell-free system (S100) ( xref )."

sparser
"Recently, a study by the Chen group reported that A20 inhibits IKK by a noncatalytic mechanism."

sparser
"A20 inhibition of IKK was dependent on A20 binding to NEMO which was induced by K63-linked polyubiquitin chains. xref The binding of A20 with NEMO occurred rapidly upon IL-1 stimulation (2–5 min) in HeLa cells. xref Therefore, the polyubiquitin chains that serve to activate IKK also serve a dual function in its negative regulation by the recruitment of A20 to NEMO."

eidos
"When NF-kappaB is activated , IkappaBs are released from the NF-kappaB DNA-binding domain , and A20 suppresses IKK activation ."