IndraLab

Statements

USP14 deubiquitinates AR. 10 / 11
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"USP14 inhibits AR ubiquitination and subsequent degradation in both prostate and breast cancer cells [77, 78]."
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"In prostate cancer, USP14 binds to androgen receptor (AR), and USP14 inhibition promotes the ubiquitination of AR and accelerates its degradation, thus inhibiting the proliferation of prostate cancer cells and arresting the cell cycle in G0/G1 phase [22]."
36604147
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"As a deubiquitinating enzyme, USP14 has previously been reported to enhance the deubiquitination of AR and resist the binding of MDM2, but the specific mechanism is still unclear and needs further exploration."
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"Moreover, AR overexpression inhibited USP14 inhibition induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR positive breast cancer."
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"Treatment of LNCaP cells with b-AP15 in androgen depleted medium decreased AR protein, but did not substantially increase levels of high molecular weight AR, indicating that unliganded AR was not being deubiquitylated by USP14 or UCHL5 (Fig. 2a)."
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"In addition, reduction of UCHL5 by its siRNA did not affect the expression of AR, suggesting that USP14 but not UCHL5 recruited on the19S proteasome plays a selective role in the deubiquitination of AR."
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"We found that IU1 and USP14 knockdown dramatically increased levels of ubiquitinated and K48 ubiquitinated AR, suggesting that USP14 is an AR DUB, capable of deubiquitinating and thereby stabilizing AR protein."
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"Treatment of control MDA-MB-453 (either scramble shRNA or parental) cells with CHX for up to 12h caused decreased levels of AR, suggesting a contribution of AR protein synthesis to endogenous AR protein levels; however, co-treatment of CHX and USP14 shRNA or IU1 resulted more rapid decrease in levels of endogenous AR protein, strongly suggest that deubiquitination of AR protein by USP14 is essential for its protein stability."
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"However, for a specific protein, such as AR, the inhibition of USP14 would impair the deubiquitination of AR, which consequently leads to the degradation of this protein."
30639309
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"Notably, USP14 has previously been reported to mediate AR deubiquitylation ."
38182874