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Auranofin inhibits UCHL5. 13 / 13
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"The loaded Auranofin in PCN224@Au could be released to down-regulate the deubiquitinating enzymes (e.g., CyclinB, USP14 and UCH37), blockade the deubiquitinating process and promote the accumulations of proteasomal substrate proteins (e.g., c-Jun and p21) to encourage proteasomal degradation of ubiquitinated target proteins."
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"AF may also elicit cytotoxicity in cancer cells by disrupting protein homeostasis (proteostasis) via proteasomal inhibition, in particular, by targeting the 19 S proteasome-associated deubiquitinases (DUBs), UCHL5, and USP14 [7–9]."
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"Hence, we speculated that Aur inhibited androgen receptor signaling by PKC pathway and promoted the degradation of androgen receptor result from USP14 and UCHL5 inhibition.Interestingly, inhibition of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Interestingly, we found that different from bortezomib, AF inhibits 19S proteasome associated DUBs UCHL5 and USP14 but not the 20S proteasome activity."
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"In detail, Auranofin release from PCN224@Au down-regulated the deubiquitinating enzymes (e.g., CyclinB, USP14 and UCH37) and promoted the proteasomal substrate proteins (e.g., c-Jun and p21) accumulations via activating MAP3Ks, CDK and p53 pathways, which drove ubiquitinated target degradation by proteasome."
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"Auranofin (Aur) inhibits proteasome associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; inhibition of the proteasome associated DUBs is required for Aur induced cytotoxicity; and Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from patients with acute myeloid leukemia [XREF_BIBR]."
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"It has been documented that Auranofin inhibits the deubiquitinating enzymes, UCHL5/UCH37 and USP14/Ubp6 that belong to cysteine proteases of the UCH and USP families, respectively, thereby affecting the proteasome activity."
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"This was also confirmed by computational molecular docking, K48 linked polyubiquitin disassembly, and HA-UbVS competitive binding assay; these experiments showed that AF might inhibit the proteasomal cysteine DUBs UCHL5 and USP14."
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"Considering previous reports [ 16 ] we further investigated whether auranofin inhibits proteasome DUBs (USP14/UCHL5) of the 19S regulatory particle."
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"A previous study has reported that AF indeed inhibits proteasome-associated DUBs, UCHL5 and USP14."
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"The computational model also indicates that an active metabolite of auranofin can inhibit UCHL5 and USP14."
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"Interestingly, we found that different from bortezomib, AF inhibits 19S proteasome-associated DUBs UCHL5 and USP14 but not the 20S proteasome activity."
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"HA-UbVS pretreatment of auranofin could bind the HA tagged UbVS in the purified 26S proteasome, supporting that auranofin inhibits UCHL5 and USP14."
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