* Systems level-based RNAi screening by high content analysis identifies UBR5 as a regulator of estrogen receptor-α protein levels and activity.
- Estrogen receptor-α (ERα) is a central transcription factor that regulates mammary gland physiology and a key driver in breast cancer. In the present study, we aimed to identify novel modulators of ERα-mediated transcriptional regulation via a custom-built siRNA library screen. This screen was directed against a variety of coregulators, transcription modifiers, signaling molecules and DNA damage response proteins. By utilizing a microscopy-based, multi-end point, estrogen responsive biosensor cell line platform, the primary screen identified a wide range of factors that altered ERα protein levels, chromatin remodeling and mRNA output. We then focused on UBR5, a ubiquitin ligase and known oncogene that modulates ERα protein levels and transcriptional output. Finally, we demonstrated that UBR5 also affects endogenous ERα target genes and E2-mediated cell proliferation in breast cancer cells. In conclusion, our multi-end point RNAi screen identified novel modulators of ERα levels and activity, and provided a robust systems level view of factors involved in mechanisms of nuclear receptor action and pathophysiology. Utilizing a high throughput RNAi screening approach we identified UBR5, a protein commonly amplified in breast cancer, as a novel regulator of ERα protein levels and transcriptional activity.
Overview of verb demonstrate
The verb demonstrate has 4 senses (first 4 from tagged texts)
1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested
audience; "She shows her dogs frequently"; "We will demo the new software in Washington")
2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an
example, explanation or experiment; "The experiment demonstrated the instability of the compound";
"The mathematician showed the validity of the conjecture")
3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of;
show by one's behavior, attitude, or external attributes; "His high fever attested to his illness";
"The buildings in Rome manifest a high level of architectural sophistication"; "This decision
demonstrates his sense of fairness")
4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands
demonstrated against globalization during the meeting of the most powerful economic nations in
Seattle")
Overview of adj demonstrated
The adj demonstrated has 1 sense (first 1 from tagged texts)
1. (1) demonstrated -- (having been demonstrated or verified beyond doubt)
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