IndraLab

Statements

USP22 activates AR. 19 / 25
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"Given the ability of USP22 to enhance AR accumulation, AR activity, and CRPC, the biological impact of a model of tetracycline inducible shUSP22 was developed in therapy sensitive PCa cells."
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"These data suggest that USP22 functions to enhance AR stability and promote inappropriate castration resistant AR signaling through proteasome dependent regulation of AR levels."
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"Based on the data above, suppression of USP22 in models of ADT sensitive PCa and aggressive CRPC decreased the AR signaling axis (XREF_FIG and XREF_FIG)."
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"By contrast, USP22 deregulation induced marked enhancement of ligand independent AR activity, determined by analyses of multiple, clinically relevant AR target genes (XREF_FIG)."
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"One important distinction is that previous findings are largely based on reporter assays analyzing USP22 mediated AR transactivation in Drosophila and human embryonic kidney (HEK) cells, and AR expression perturbation under conditions of ectopic overexpression of AR and USP22 in HEK cells."
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"USP22 modulates both AR and MYC activity [ 8] , and USP22 mRNA expression was positively correlated with both AR and MYC mRNA expression ( p = 7.76e-14 and p =3 .36 e-7 , respectively ; Figure 1B ) , further supporting a pro-oncogenic role for USP22 in tumors with elevated AR and MYC expression ."
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"USP22, ATXN7L3, and ENY2 significantly enhanced AR mediated transactivation in the presence of ligand (2.5- to 3.5-fold compared to AR alone), similarly to the effect of the GCN5 HAT."
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"Together, these data demonstrate that USP22 regulates ligand independent AR residence at target gene loci and promotes AR driven CRPC gene profiles, which may have specificity for USP22 perturbation, further implicating USP22 as an independent effector of aggressive tumor phenotypes."
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"These data demonstrate that USP22 potentiates both ligand dependent and ligand independent AR function."
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"In addition, USP22 expression was shown to increase the abundance of c-Myc and the androgen receptor itself [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"Moreover, USP22 and DHT acted cooperatively to further enhance AR activity (XREF_FIG)."
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"Strikingly, USP22 deregulation significantly increased AR occupancy at known ARORs (1.15-2.6% input; XREF_FIG), but not in control regions of the KLK3 and PSA (' EF ' region, XREF_SUPPLEMENTARY)."
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"USP22 Enhances AR Activity and Promotes Bypass of AR Antagonists."
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"Indeed, USP22 upregulates the abundance of the androgen receptor by protecting it from proteasomal degradation through deubiquitination [XREF_BIBR]."
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"AR stability was enhanced by USP22, whereby the AR half-life was extended from 14 hours (LN-Vec) to 18 hours (LN-USP22) (XREF_FIG)."
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"In addition to the role of USP22 in the cell cycle, USP22 promotes the activity of the androgen receptor (AR)."
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"These data put forth the provocative hypothesis that USP22 increases the activity of AR through altering AR protein levels, thus identifying a novel role for USP22 in modulating steroid receptor function."
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"Therefore it is possible that RNF6 and USP22 contribute to prostate cancer progression by changing AR activity and stability."
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"In multiple xenograft models of human cancer, modeling of tumor associated USP22 deregulation demonstrated that USP22 controls androgen receptor accumulation and signaling, and that it enhances expression of critical target genes coregulated by androgen receptor and MYC."
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