Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G

Zibo Zhao, Lu Wang, Taryn James, Youngeun Jung, Ikyon Kim, Renxiang Tan, F. Michael Hoffmann, Wei Xu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

ERβ is regarded as a "tumor suppressor" in breast cancer due to its anti-proliferative effects. However, unlike ERα, ERβ has not been developed as a therapeutic target in breast cancer due to loss of ERβ in aggressive cancers. In a small-molecule library screen for ERβ stabilizers, we identified Diptoindonesin G (Dip G), which significantly increases ERβ protein stability while decreasing ERα protein levels. Dip G enhances the transcription and anti-proliferative activities of ERβ, while attenuating the transcription and proliferative effects of ERα. Further investigation revealed that instead of targeting ER, Dip G targets the CHIP E3 ubiquitin ligase shared by ERα and ERβ. Thus, Dip G is a dual-functional moiety that reciprocally controls ERα and ERβ protein stability and activities via an indirect mechanism. The ERβ stabilization effects of Dip G may enable the development of ERβ-targeted therapies for human breast cancers.

Original languageEnglish
Pages (from-to)1608-1621
Number of pages14
JournalChemistry and Biology
Volume22
Issue number12
DOIs
Publication statusPublished - 2015 Dec 17

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G'. Together they form a unique fingerprint.

  • Cite this

    Zhao, Z., Wang, L., James, T., Jung, Y., Kim, I., Tan, R., Hoffmann, F. M., & Xu, W. (2015). Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G. Chemistry and Biology, 22(12), 1608-1621. https://doi.org/10.1016/j.chembiol.2015.10.011