Involvement of retinoic acid/retinoid receptors in the regulation of murine αB-crystallin/small heat shock protein gene expression in the lens

Rashmi Gopal-Srivastava, Ales Cvekl, Joram Piatigorsky

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Crystallins are a diverse group of abundant soluble proteins that are responsible for the refractive properties of the transparent eye lens. We showed previously that Pax-6 can activate the αB-crystallin/small heat shock protein promoter via the lens-specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46). Here we demonstrate that retinoic acid can induce the accumulation of αB-crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers (retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid response elements within LSR1 and LSR2. Electrophoretic mobility shift assays using antibodies indicated that LSR1 and LSR2 can interact with endogenous RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together had an additive effect on the activation of αB-promoter in the transfected lens cells. Thus, the αB- crystallin gene is activated by Pax-6 and retinoic acid receptors, making these transcription factors examples of proteins that have critical roles in early development as well as in the expression of proteins characterizing terminal differentiation.

Original languageEnglish (US)
Pages (from-to)17954-17961
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number28
DOIs
StatePublished - Jul 10 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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