IndraLab

Statements

COPS5 activates TP53. 19 / 23
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"Jab1 induces the cytoplasmic localization and degradation of p53 in coordination with Hdm2."
16624822
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"The nuclear and cytoplasmic co-localization between COPS5 and p53 suggests a mechanism of COPS5 and p53 interaction and relocalization of p53 from the nucleus to the cytoplasm, and treatment of MG132, a potent proteasome inhibitor, significantly inhibited proteasome dependent protein degradation of p53 and enhanced its levels in cytoplasm, which indicated the degradation of p53 induced by COPS5."
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"When Jab1 was co-expressed with S149D and T150E, their nuclear export pattern was similar to wild-type p53, and was inhibited by curcumin, suggesting that S149 and T150 on p53 are dispensable for Jab1 mediated p53 translocation (XREF_FIG and XREF_SUPPLEMENTARY, panels 1-12 and 21-32)."
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"Consistently, we found that p53 induced by curcumin or CSN5 RNAi was lack of obvious transcriptional activity."
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"Thus, we hypothesize that the increased BMP signaling activity in Jab1 cKO chondrocytes might also enhance p53 transcriptional activity, which leads to the activation of p53 downstream targets Puma, Bax, and cleaved caspase 3 (Figure 8)."
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"We next assessed the effects of curcumin on the Jab1 mediated p53 nuclear export in the U2OS osteoblastoma cell line harboring intact p53."
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"Interestingly, curcumin treatment significantly inhibited Jab1 mediated p53 cytoplasmic localization with only 16% of the cells displaying p53 in the cytoplasm (XREF_FIG, panels 13-16)."
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"CSN5 and Jab1 elimination inhibited progression of the cell cycle at multiple points, seemed to initiate p53 independent senescence and increased the ploidy of cells."
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"The substitution of threonine 155 for valine (T155V) abrogated Jab1 mediated p53 nuclear export, indicating that phosphorylation at this site is essential for Jab1 mediated regulation of p53."
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"We therefore used curcumin, a CSN associated kinase inhibitor, to test whether CSN dependent phosphorylation is involved in Jab1 mediated p53 regulation."
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"Curcumin prevents Jab1 mediated p53 nuclear export."
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"Phosphorylation of Thr 155 on p53 is required for Jab1 mediated p53 nuclear export."
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"Here, we show that phosphorylation at the threonine 155 residue is essential for Jab1 mediated p53 nuclear export."
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"Similarly, knockdown of UCH37 and USP14 or b-AP15 treatment rescued p53 protein, induced by COPS5 overexpression, and enhanced the activity of transfected luciferase reporter plasmids for p53, Bax, and p21 expression and protein levels of p53 downstream target genes BAX and p21."
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"Significantly, inhibition of CSN associated kinase activity or knockdown of CSN5 impairs JFK promoted p53 degradation, enhances p53 dependent transcription, and promotes cell growth suppression, G (1) arrest, and apoptosis."
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"Cell fractionation analysis further supported our finding that ectopic Jab1 expression induced p53 accumulation in the cytoplasm, and this was reversed by curcumin treatment (XREF_FIG)."
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"CSN5 and Jab1 is also thought to promote degradation of p53 tumor suppressor via phosphorylation by a CSN associated protein kinase [16]."
11967155
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"To further confirm the effect of curcumin on Jab1 mediated p53 nuclear export, the nucleus and cytoplasm of cells were fractionated and analyzed by western blotting."
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"JAB1 induces p53 cytoplasmic localization and its subsequent degradation, which helps to maintain low levels of p53 under normal conditions XREF_BIBR, XREF_BIBR, XREF_BIBR."
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