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

16 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

Fingerprint

Protein Stability
Transcription
Breast Neoplasms
Small Molecule Libraries
Proteins
Ubiquitin-Protein Ligases
Tumors
Neoplasms
Stabilization
diptoindonesin G
Molecules
Therapeutics

All Science Journal Classification (ASJC) codes

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

Cite this

Zhao, Zibo ; Wang, Lu ; James, Taryn ; Jung, Youngeun ; Kim, Ikyon ; Tan, Renxiang ; Hoffmann, F. Michael ; Xu, Wei. / Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G. In: Chemistry and Biology. 2015 ; Vol. 22, No. 12. pp. 1608-1621.
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Zhao, Z, Wang, L, James, T, Jung, Y, Kim, I, Tan, R, Hoffmann, FM & Xu, W 2015, 'Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G', Chemistry and Biology, vol. 22, no. 12, pp. 1608-1621. https://doi.org/10.1016/j.chembiol.2015.10.011

Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G. / Zhao, Zibo; Wang, Lu; James, Taryn; Jung, Youngeun; Kim, Ikyon; Tan, Renxiang; Hoffmann, F. Michael; Xu, Wei.

In: Chemistry and Biology, Vol. 22, No. 12, 17.12.2015, p. 1608-1621.

Research output: Contribution to journalArticle

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AU - Zhao, Zibo

AU - Wang, Lu

AU - James, Taryn

AU - Jung, Youngeun

AU - Kim, Ikyon

AU - Tan, Renxiang

AU - Hoffmann, F. Michael

AU - Xu, Wei

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