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OTUB1 activates MAPK. 11 / 14
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"Stimulation of OTUB1-competent BMDCs with both TgPFN and LPS resulted in increased p38, ERK1/2, and JNK phosphorylation compared to that in OTUB1-deficient BMDCs (Supplementary Fig. 2g, h), demonstrating that OTUB1 augments the activation of both NF-κB and MAPKs upon the engagement of TLR4 and TLR11/12."

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"First, OTUB1 promotes hyperactivation of the MAPK cascade only when overexpressed in a wt RAS background."

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"We also did not observe OTUB1 induced hyperactivation of the MAPK kinase pathway when we overexpressed a dominant negative KRAS S17N-mutant, indicating that the effect of OTUB1 overexpression is RAS dependent (XREF_SUPPLEMENTARY)."

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"Furthermore, knockdown of OTUB1 reduces TWEAK induced activation of canonical NF-kappaB and MAPK signalling pathways and modulates TWEAK induced gene expression."

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"Here we found that OTUB1 promotes tumorigenic transformation of wt RAS cells by triggering the RAS and MAPK pathway."

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"OTUB1 overexpression in the H1993 cell line harboring wt KRAS led to a higher and more sustained activation of ERK1/2 phosphorylation (Fig XREF_FIG A), whereas the introduction of OTUB1 into KRAS-mutant A549 cells only slightly increased the activity of the MAPK pathway (Fig XREF_FIG B)."

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"Consistently with our observation that OTUB1 overexpression induces the MAPK cascade activation in cells with wt RAS, we found that higher levels of OTUB1 significantly correlated with increased levels of ERK1/2 phosphorylation in lung adenocarcinomas harboring wt KRAS (Pearson 's coefficient : 0.352; P-value : 0.013) (Fig XREF_FIG D and E), while mutant KRAS tumors exhibited in general higher levels of ERK1/2 phosphorylation (Fig XREF_FIG D and E)."

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"We observed a similar overactivation of the MAPK pathway, when we overexpressed catalytically inactive OTUB1 C91S-mutant, indicating that catalytic activity of OTUB1 is not necessary to induce the MAPK pathway activation (Fig XREF_FIG F)."

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"Given that OTUB1 overexpression up-regulated the MAPK pathway, but did not affect AKT signaling, we hypothesized that OTUB1 could cooperate with myristoylated (myr) and therefore the constitutively active allele of AKT1 (myr-AKT) to promote cell transformation."

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"Hyperactivation of the MAPK signaling by OTUB1 overexpression suggests that OTUB1 overexpression may promote tumorigenic transformation."

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"On the other hand, OTUB1 did not further accelerate anchorage independent colony formation of HEK TE cells overexpressing both a constitutively active MEK1 D218, D222 allele (MEKDD) and myr-AKT, further confirming that OTUB1 overexpression promotes tumorigenic transformation by inducing the MAPK cascade activation."