IndraLab

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TCHH inhibits PSMD14. 13 / 13
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"We found that Thiolutin (THL, Figure XREF_FIG A), a disulfide containing antibiotic and anti-angiogenic compound XREF_BIBR, dramatically inhibited DUB activity of PSMD14 (compared with other JAMM DUBs) in a dose-manner dependent using Ubiquitin-AMC assay (XREF_SUPPLEMENTARY), which was in line with the results of previous studies XREF_BIBR."
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"The data of this study demonstrated that THL significantly suppressed DUB activity of PSMD14 in a dose dependent manner, while neither the protein expression nor mRNA level of PSMD14 was affected."
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"Taken together, these results indicate that THL blocks the DUB activity of PSMD14 to prevent it from interacting with SNAIL, resulting in the ubiquitination and instability of SNAIL."
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"It is possible that free AMC was still produced by Rpn8, which is also a DUB, even though Rpn11 was inhibited by THL."
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"In addition, THL also prevented PSMD14 from interacting with SNAIL."
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"Despite of the potential inhibition on other JAMM proteases at high concentration, THL could inhibit PSMD14 with a minimum IC 50 XREF_BIBR."
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"Overall, these findings indicate that THL could serve as a promising adjuvant to increase chemosensitivity in HNSCC by targeting PSMD14."
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"Addition of Zn(cyclen) 2+ in excess over THL abrogated inhibition of Rpn11 ( xref ), suggesting that THL inhibits Rpn11 by binding of Zn 2+ ."
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"Moreover, we performed in vivo ubiquitination assay and found that THL greatly elevated the poly-ubiquitination of SNAIL, reconfirming that THL suppresses DUB activity of PSMD14."
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"Besides, the mRNA level of PSMD14 was not affected significantly in both ESCC cell lines tested, indicating that THL only inhibited the DUB activity of PSMD14."
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"Despite of the potential inhibition on other JAMM proteases at high concentration, THL could inhibit PSMD14 with a minimum IC 50 xref ."
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"Together the data indicate that THL inhibits Rpn11 via chelation of its Zn 2+ - ion."
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"In this study, we found that THL dramatically suppressed the DUB activity of PSMD14 (with little effect on other JAMM DUBs) and E2F1/Akt/SOX2 pathway, which spurred tremendous interests to exploit THL as an anti-tumor drug."
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