IndraLab

Statements

COPS5 inhibits NCOR. 9 / 9
| 9
reach
"To further evaluate the role of COP9 complex in COPS5 mediated NCoR protein degradation, we examined the role of some COP9 subunits by RNAi."
27375289
reach
"However, when COPS5 is amplified and overexpressed in endocrine resistant cancer cells, elevated COPS5 and COP9 activity induces global NCoR protein degradation."
27375289
reach
"Low basal level of COP9 and COPS5 is associated with NCoR and constantly degrade and recycle the NCoR complex as part of the repression strategy to prevent coactivator recruitment, similar to the mechanism of cyclical activation XREF_BIBR XREF_BIBR."
27375289
reach
"Therefore, tamoxifen retains as an antagonist; (2) in tamoxifen resistant cells, NCoR is globally diminished by degradation due to COPS5 overexpression and consequently high levels of COP9 and COPS5 activity."
27375289
reach
"It is also confirmed that overexpression of Jab1 and COPS5 degrades NCoR protein through the ubiquitination-proteasome pathway in breast cancer."
29535627
reach
"Satisfyingly, COPS5 reduction and subsequent NCoR upregulation by COPS5 shRNA were observed at the end point of doxycycline and tamoxifen-treatment at day 42 in vivo (XREF_SUPPLEMENTARY, last two lanes)."
27375289
reach
"Interestingly, overexpression of COPS5 induces ubiquitination and proteasomal degradation of the NCoR protein, a key corepressor of tamoxifen bound ERalpha, leading to de-repression of ERalpha target genes in resistant breast cancer (XREF_FIG, XREF_FIG, XREF_FIG, XREF_FIG)."
27375289
reach
"However, in 4OHT resistant MCF7 cells, neither NCoR nor COP9 was recruited, whereas ERalpha and PCAF were able to bind to the promoter on 4OHT-treatment (XREF_FIG, black bars), due probably to global loss of NCoR by overexpression of COPS5."
27375289
reach
"Next, we noticed that NCoR protein, rather than mRNA, was downregulated by overexpression of WT COPS5 in parental MCF7 cells (XREF_FIG, XREF_SUPPLEMENTARY)."
27375289