IndraLab

Statements


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sparser
"Here we demonstrate that TRE17 activates canonical p65-containing NF-κB through an atypical mechanism that is independent of IκB phosphorylation/degradation."

sparser
"IκB-SR completely abrogated activation of NF-κB by TRE17 as determined by EMSA ( xref )."

reach
"We previously reported that USP6 activates NF-kappaB, and that NF-kappaB plays an essential role in USP6 mediated transformation."

eidos
"In these models , activation of STAT3 , NF-kappaB , and beta-catenin by USP6 was essential for tumorigenesis , as genetic or pharmacologic inhibition of these pathways significantly attenuated xenograft growth ( 16 , 23 , 24 ) ."

sparser
"In these models, activation of STAT3, NF-κB, and β-catenin by USP6 was essential for tumorigenesis, as genetic or pharmacologic inhibition of these pathways significantly attenuated xenograft growth ( xref , xref , xref )."

sparser
"We recently reported that TRE17 activates NF-κB, in a manner dependent on its USP activity ( xref )."

sparser
"Optimal activation of NF-κB by TRE17 requires both catalytic subunits of IKK, distinguishing its mechanism from the classical and non-canonical pathways, which require either IKKβ or IKKα, respectively."

reach
"This USP6 dependent activation of NF-kappaB requires IKKalpha, IKKbeta and NEMO in order for p65 S536 phosphorylation to take place."

sparser
"We recently reported that activation of NF-κB by TRE17 is mediated in part by RhoA and ROCK ( xref )."

reach
"Activation of NF-kappaB by USP6 was completely suppressed in these cells (XREF_FIG, left), in accordance with our previous results."

sparser
"In aggregate these data indicate that TRE17(long) activates classical NF-κB through a mechanism that does not appear to involve phosphorylation and degradation of IκB."

sparser
"This USP6 dependent activation of NF-κB requires IKKα, IKKβ and NEMO in order for p65 S536 phosphorylation to take place."

sparser
"In the current study we examine the mechanism by which it functions, demonstrating that TRE17 activates classical NF-κB through an atypical mechanism that is independent of IκB degradation."

sparser
"However, the mechanism by which TRE17 activates NF-κB and the selective involvement of the classical vs. non-canonical pathways were not examined."

sparser
"Together, these data suggest that TRE17 activates NF-κB by promoting S536 phosphorylation of p65, in manner that optimally requires IKKα, IKKβ, and NEMO."

sparser
"We next sought to determine which IKK subunits were required for activation of NF-κB by TRE17."

sparser
"Activation of NF-κB by USP6 was completely suppressed in these cells ( xref , left), in accordance with our previous results ( xref )."

sparser
"The findings above suggest that TRE17(long) may activate NF-κB by regulating nuclear translocation of an IκB-free population of p65."

sparser
"In sum, these data indicate that TRE17(long) selectively activates classical NF-κB, consisting of either homo- or heterodimeric p65 complexes, in three different cell types."

sparser
"Our finding that TRE17 activates classical NF-κB in the absence of IκB degradation, and in a manner requiring both IKKα and IKKβ, adds to the growing list of stimuli that activate NF-κB through mechanisms distinct from simplified depiction of the classical pathway ( xref ; xref )."

sparser
"TRE17 activates canonical NF-κB independently of IκB phosphorylation and degradation."

sparser
"To determine whether TRE17 activates classical or non-canonical NF-κB, electrophoretic mobility shift assays (EMSAs) were performed."

reach
"However, only one DUB, TRE17 and USP6, has been shown to induce NF-kappaB activation 27."

reach
"This validates our cellular model systems, and indicates that USP6 expression in human tumors triggers STAT3 and NF-kappaB signaling responses."

sparser
"In summary, these studies uncover an unexpected signaling mechanism for activation of classical NF-κB by TRE17."

sparser
"We previously reported that USP6 activates NF-κB, and that NF-κB plays an essential role in USP6-mediated transformation ( xref , xref )."

sparser
"Although IκB degradation is not normally elicited by TRE17, we speculated that overexpression of the IκB Super Repressor (IκB-SR) might nevertheless effectively sequester p65 and block NF-κB activation by TRE17(long)."

sparser
"We next examined whether activation of NF-κB by TRE17 was required for tumorigenesis."

sparser
"These results indicate that IKKβ, NEMO and, unexpectedly, IKKα all contribute to activation of NF-κB by TRE17(long)."

sparser
"Since inhibition of RhoA/ROCK only partially attenuated activation of NFκB by TRE17, this suggests that TRE17 functions through additional parallel pathways, in a manner that requires its USP activity."