The Regulator of Calcineurin 1 (RCAN1/DSCR1) Activates the CAMP Response Element-binding Protein (CREB) Pathway

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Sep 6

PMID 21890628

Citations 14

Authors

Seon Sook Kim

Su Ryeon Seo

Affiliations

Soon will be listed here.

Abstract

cAMP response element-binding protein (CREB) is one of the best known transcription factors in the development and function of the nervous system. In this report, we found that the regulator of calcineurin 1 (RCAN1), which is overexpressed in the brain of patients with Down syndrome, increased the phosphorylation of CREB and cAMP response element-mediated gene transcription in response to the activation of the intracellular cAMP pathway. Furthermore, we found that the increased activation of CREB signaling by RCAN1 depended on the ability of RCAN1 to inhibit calcineurin activity. Our data provide the first evidence that RCAN1 acts as an important regulatory component in the control of CREB signaling.

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References

Mansuy I, Mayford M, Jacob B, Kandel E, Bach M . Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell. 1998; 92(1):39-49. DOI: 10.1016/s0092-8674(00)80897-1. View

Hagiwara M, Alberts A, Brindle P, Meinkoth J, Feramisco J, Deng T . Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell. 1992; 70(1):105-13. DOI: 10.1016/0092-8674(92)90537-m. View

Rothermel B, Vega R, Yang J, Wu H, Bassel-Duby R, Williams R . A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling. J Biol Chem. 2000; 275(12):8719-25. DOI: 10.1074/jbc.275.12.8719. View

Kingsbury T, Bambrick L, Roby C, Krueger B . Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. J Neurochem. 2007; 103(2):761-70. DOI: 10.1111/j.1471-4159.2007.04801.x. View

Mansuy I, Winder D, Moallem T, Osman M, Mayford M, Hawkins R . Inducible and reversible gene expression with the rtTA system for the study of memory. Neuron. 1998; 21(2):257-65. DOI: 10.1016/s0896-6273(00)80533-4. View

Liu F, Grundke-Iqbal I, Iqbal K, Oda Y, Tomizawa K, Gong C . Truncation and activation of calcineurin A by calpain I in Alzheimer disease brain. J Biol Chem. 2005; 280(45):37755-62. DOI: 10.1074/jbc.M507475200. View

Sheng M, Greenberg M . The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron. 1990; 4(4):477-85. DOI: 10.1016/0896-6273(90)90106-p. View

Ji L, Mochon E, Arcinas M, Boxer L . CREB proteins function as positive regulators of the translocated bcl-2 allele in t(14;18) lymphomas. J Biol Chem. 1996; 271(37):22687-91. DOI: 10.1074/jbc.271.37.22687. View

Ahn S, Olive M, Aggarwal S, Krylov D, Ginty D, Vinson C . A dominant-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos. Mol Cell Biol. 1998; 18(2):967-77. PMC: 108809. DOI: 10.1128/MCB.18.2.967. View

10.

Dodge K, Scott J . Calcineurin anchoring and cell signaling. Biochem Biophys Res Commun. 2003; 311(4):1111-5. DOI: 10.1016/j.bbrc.2003.09.040. View

11.

Fuentes J, Pritchard M, Planas A, Bosch A, Ferrer I, Estivill X . A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart. Hum Mol Genet. 1995; 4(10):1935-44. DOI: 10.1093/hmg/4.10.1935. View

12.

Cho K, Kim Y, Cho Y, Kim S . Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke. Exp Neurol. 2008; 212(1):85-92. DOI: 10.1016/j.expneurol.2008.03.017. View

13.

Reeves R, Irving N, Moran T, WOHN A, Kitt C, Sisodia S . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995; 11(2):177-84. DOI: 10.1038/ng1095-177. View

14.

Pittenger C, Huang Y, Paletzki R, Bourtchouladze R, Scanlin H, Vronskaya S . Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory. Neuron. 2002; 34(3):447-62. DOI: 10.1016/s0896-6273(02)00684-0. View

15.

Shioda N, Moriguchi S, Shirasaki Y, Fukunaga K . Generation of constitutively active calcineurin by calpain contributes to delayed neuronal death following mouse brain ischemia. J Neurochem. 2006; 98(1):310-20. DOI: 10.1111/j.1471-4159.2006.03874.x. View

16.

KING M, Huang C, Chock P, Nairn A, Hemmings Jr H, Chan K . Mammalian brain phosphoproteins as substrates for calcineurin. J Biol Chem. 1984; 259(13):8080-3. View

17.

Deak M, Clifton A, Lucocq L, Alessi D . Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998; 17(15):4426-41. PMC: 1170775. DOI: 10.1093/emboj/17.15.4426. View

18.

Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J . Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet. 2001; 10(18):1915-23. DOI: 10.1093/hmg/10.18.1915. View

19.

Enslen H, Sun P, Brickey D, Soderling S, Klamo E, Soderling T . Characterization of Ca2+/calmodulin-dependent protein kinase IV. Role in transcriptional regulation. J Biol Chem. 1994; 269(22):15520-7. View

20.

Hoeffer C, Dey A, Sachan N, Wong H, Patterson R, Shelton J . The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling. J Neurosci. 2007; 27(48):13161-72. PMC: 6673398. DOI: 10.1523/JNEUROSCI.3974-07.2007. View