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USP6 activates NFkappaB. 31 / 31
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"The upregulation of USP6 expression is considered to initiate osteoblastic tumorigenesis by triggering NF-kappa-B activation and contributing to the osteolytic and inflammatory processes typically obs[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"IκB-SR completely abrogated activation of NF-κB by TRE17 as determined by EMSA ( xref )."
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"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."
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"The findings above suggest that TRE17(long) may activate NF-κB by regulating nuclear translocation of an IκB-free population of p65."
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"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."
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"We recently reported that TRE17 activates NF-κB, in a manner dependent on its USP activity ( xref )."
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"However, the mechanism by which TRE17 activates NF-κB and the selective involvement of the classical vs. non-canonical pathways were not examined."
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"To determine whether TRE17 activates classical or non-canonical NF-κB, electrophoretic mobility shift assays (EMSAs) were performed."
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"Here we demonstrate that TRE17 activates canonical p65-containing NF-κB through an atypical mechanism that is independent of IκB phosphorylation/degradation."
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"We next sought to determine which IKK subunits were required for activation of NF-κB by TRE17."
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"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."
20418905
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"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."
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"TRE17 activates canonical NF-κB independently of IκB phosphorylation and degradation."
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"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 ) ."
33558334
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"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 )."
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"We recently reported that activation of NF-κB by TRE17 is mediated in part by RhoA and ROCK ( xref )."
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"However, only one DUB, TRE17 and USP6, has been shown to induce NF-kappaB activation 27."
30194441
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"These results indicate that IKKβ, NEMO and, unexpectedly, IKKα all contribute to activation of NF-κB by TRE17(long)."
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"We previously reported that USP6 activates NF-κB, and that NF-κB plays an essential role in USP6-mediated transformation ( xref , xref )."
27440725
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"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)."
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"Activation of NF-κB by USP6 was completely suppressed in these cells ( xref , left), in accordance with our previous results ( xref )."
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"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 )."
33558334
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"This USP6 dependent activation of NF-kappaB requires IKKalpha, IKKbeta and NEMO in order for p65 S536 phosphorylation to take place."
26999213
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"Together, these data suggest that TRE17 activates NF-κB by promoting S536 phosphorylation of p65, in manner that optimally requires IKKα, IKKβ, and NEMO."
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"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."
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"We previously reported that USP6 activates NF-kappaB, and that NF-kappaB plays an essential role in USP6 mediated transformation."
27440725
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"This validates our cellular model systems, and indicates that USP6 expression in human tumors triggers STAT3 and NF-kappaB signaling responses."
27440725
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"This USP6 dependent activation of NF-κB requires IKKα, IKKβ and NEMO in order for p65 S536 phosphorylation to take place."
26999213
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"Activation of NF-kappaB by USP6 was completely suppressed in these cells (XREF_FIG, left), in accordance with our previous results."
27440725
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"In summary, these studies uncover an unexpected signaling mechanism for activation of classical NF-κB by TRE17."
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"We next examined whether activation of NF-κB by TRE17 was required for tumorigenesis."
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