FEBS Letters
Volume 583, Issue 19 , Pages 3140-3144, 6 October 2009

Activation of adenylate cyclase by forskolin increases the protein stability of RCAN1 (DSCR1 or Adapt78)

Edited by Noboru Mizushima

  • Su Ryeon Seo

      Affiliations

    • Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea
    • Corresponding Author InformationCorresponding authors. Fax: +82 33 241 4627 (S.R. Seo), +82 2 312 5657 (K.C. Chung).
    • ,
  • Seon Sook Kim

      Affiliations

    • Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea
    • ,
  • Kwang Chul Chung

      Affiliations

    • Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea
    • Corresponding Author InformationCorresponding authors. Fax: +82 33 241 4627 (S.R. Seo), +82 2 312 5657 (K.C. Chung).

Received 13 July 2009; received in revised form 8 September 2009; accepted 9 September 2009. published online 14 September 2009.

Abstract 

Overexpression of Regulator of Calcineurin 1 (RCAN1/DSCR1/Adapt78) is known to inhibit the calcineurin-NFAT dependent signaling pathway. In this report, we find that activation of adenylate cyclase by forskolin increases the expression of RCAN1 through the increase of the protein’s half-life. The ability of forskolin to increase the accumulation of RCAN1 protein is significantly inhibited with protein kinase A inhibitors such as KT5720 and H-89. Furthermore, forskolin targets the central and C-terminal region of RCAN1 and enhances the inhibitory effect of RCAN1 on the calcineurin-mediated activation of NFAT. Our findings provide the first evidence that the accumulation of the RCAN1 protein by cAMP acts as an important regulatory mechanism in the control of the calcineurin-dependent cellular pathway.

Structured summary

MINT-7262390: PKA (uniprotkb:P22694) phosphorylates (MI:0217) RCAN1 (uniprotkb:P53805) by protein kinase assay (MI:0424)

Abbreviations: RCAN1, Regulator of Calcineurin 1, PKA, protein kinase A, PMA, phorbol myristate acetate

Keywords: Regulator of Calcineurin 1, Forskolin, Cyclic AMP, Calcineurin, NFAT

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PII: S0014-5793(09)00707-8

doi:10.1016/j.febslet.2009.09.019

FEBS Letters
Volume 583, Issue 19 , Pages 3140-3144, 6 October 2009

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