High-content analysis of proapoptotic EphA4 dependence receptor functions using small-molecule libraries

Claudiu M. Nelersa, Henry Barreras, Erik Runko, Jerome Ricard, Yan Shi, Stephanie J. Glass, John Bixby, Vance Lemmon, Daniel J Liebl

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Small-molecule compounds (SMCs) can provide an inexpensive and selective approach to modifying biological responses. High-content analysis (HCA) of SMC libraries can help identify candidate molecules that inhibit or activate cellular responses. In particular, regulation of cell death has important implications for many pathological conditions. Dependence receptors are a new classification of proapoptotic membrane receptors that, unlike classic death receptors, initiate apoptotic signals in the absence of their ligands. EphA4 has recently been identified as a dependence receptor that may have important functions in conditions as disparate as cancer biology and CNS injury and disease. To screen potential candidate SMCs that inhibit or activate EphA4-induced cell death, HCA of an SMC library was performed using stable EphA4-expressing NIH 3T3 cells. Our results describe a high-content method for screening dependence receptor-signaling pathways and demonstrate that several candidate SMCs can inhibit EphA4-mediated cell death.

Original languageEnglish
Pages (from-to)785-795
Number of pages11
JournalJournal of Biomolecular Screening
Volume17
Issue number6
DOIs
StatePublished - Jul 1 2012

Fingerprint

EphA4 Receptor
Small Molecule Libraries
Cell Death
Molecules
Cell death
NIH 3T3 Cells
Death Domain Receptors
Central Nervous System Diseases
Ligands
Membranes
Wounds and Injuries
Neoplasms
Screening

Keywords

  • apoptosis
  • dependence receptor
  • Eph receptors
  • ephrins
  • high-content screen

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

Cite this

High-content analysis of proapoptotic EphA4 dependence receptor functions using small-molecule libraries. / Nelersa, Claudiu M.; Barreras, Henry; Runko, Erik; Ricard, Jerome; Shi, Yan; Glass, Stephanie J.; Bixby, John; Lemmon, Vance; Liebl, Daniel J.

In: Journal of Biomolecular Screening, Vol. 17, No. 6, 01.07.2012, p. 785-795.

Research output: Contribution to journalArticle

Nelersa, Claudiu M. ; Barreras, Henry ; Runko, Erik ; Ricard, Jerome ; Shi, Yan ; Glass, Stephanie J. ; Bixby, John ; Lemmon, Vance ; Liebl, Daniel J. / High-content analysis of proapoptotic EphA4 dependence receptor functions using small-molecule libraries. In: Journal of Biomolecular Screening. 2012 ; Vol. 17, No. 6. pp. 785-795.
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