Protein Phosphatases 1 and 2A Regulate the Transcriptional and DNA Binding Activities of Retinoic Acid Receptors (*)

To determine which factors may regulate the DNA binding and transcriptional properties of retinoic acid receptors (RARs and RXRs), we investigated the sensitivity of reporter genes bearing various retinoic acid response elements (RAREs) to protein phosphatases (PPases) inhibition. PPases inhibition by okadaic acid led to an increase of the reporter genes activity in a RARE-dependent and ligand-independent manner and was dependent on the type of response element used. Overexpression of protein phosphatases 2A and 1 (PP2A and PP1) decreased the inducibility of the reporter genes tested. Nuclear extracts from okadaic acid-treated COS cells displayed an 2-5-fold increased level of receptor binding to RAREs in vitro, suggesting that PPases inhibition increased the DNA binding activity of retinoid receptors. Treatment of receptors extracted from COS cells by alkaline phosphatase and partially purified PP1 and PP2A decreased their DNA binding activity, but heterodimers bound to DNA were not sensitive to phosphatase treatment. Reconstitution experiments showed that phosphorylation of both receptors increased the DNA binding activity of RXR/RAR heterodimers. Taken together, these data show that the modulation of the phosphorylation state of RARs and RXRs represents an other level of regulation of the retinoid signaling pathway.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-05-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.270.18.10806PMID 7738017
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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