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

Su Ryeon Seo; Seon Sook Kim; Kwang Chul Chung

doi:10.1016/j.febslet.2009.09.019

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

Su Ryeon Seo, Seon Sook Kim, Kwang Chul Chung

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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).

Original language	English
Pages (from-to)	3140-3144
Number of pages	5
Journal	FEBS Letters
Volume	583
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2009.09.019
Publication status	Published - 2009 Oct 6

Bibliographical note

Funding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government ( KRF-2006-331-C00239 ), 2007 Research Grant from Kangwon National University , and by the Brain Korea 21 program . This study was also supported by grants from the Korea Science and Engineering Foundation (KOSEF) ( R11-2007-040-01005-0 ), through National Research Laboratory Program ( R04-2007-000-20014-0 ) funded by Ministry of Education, Science and Technology (MEST), and from the Korea Health 21 R&D Project ( A080551 ) funded by Ministry of Health, Welfare and Family Affairs . This work was carried out in facilities of Institute of Bioscience and Biotechnology at Kangwon National University.

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

Access to Document

10.1016/j.febslet.2009.09.019

Cite this

@article{0286ac2482f6494ea5bfe8232e39c501,

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

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).",

author = "Seo, {Su Ryeon} and Kim, {Seon Sook} and Chung, {Kwang Chul}",

note = "Funding Information: This work was supported by the Korea Research Foundation Grant funded by the Korean Government ( KRF-2006-331-C00239 ), 2007 Research Grant from Kangwon National University , and by the Brain Korea 21 program . This study was also supported by grants from the Korea Science and Engineering Foundation (KOSEF) ( R11-2007-040-01005-0 ), through National Research Laboratory Program ( R04-2007-000-20014-0 ) funded by Ministry of Education, Science and Technology (MEST), and from the Korea Health 21 R&D Project ( A080551 ) funded by Ministry of Health, Welfare and Family Affairs . This work was carried out in facilities of Institute of Bioscience and Biotechnology at Kangwon National University.",

year = "2009",

month = oct,

day = "6",

doi = "10.1016/j.febslet.2009.09.019",

language = "English",

volume = "583",

pages = "3140--3144",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "19",

}

TY - JOUR

T1 - Activation of adenylate cyclase by forskolin increases the protein stability of RCAN1 (DSCR1 or Adapt78)

AU - Seo, Su Ryeon

AU - Kim, Seon Sook

AU - Chung, Kwang Chul

N1 - Funding Information: This work was supported by the Korea Research Foundation Grant funded by the Korean Government ( KRF-2006-331-C00239 ), 2007 Research Grant from Kangwon National University , and by the Brain Korea 21 program . This study was also supported by grants from the Korea Science and Engineering Foundation (KOSEF) ( R11-2007-040-01005-0 ), through National Research Laboratory Program ( R04-2007-000-20014-0 ) funded by Ministry of Education, Science and Technology (MEST), and from the Korea Health 21 R&D Project ( A080551 ) funded by Ministry of Health, Welfare and Family Affairs . This work was carried out in facilities of Institute of Bioscience and Biotechnology at Kangwon National University.

PY - 2009/10/6

Y1 - 2009/10/6

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=70349602934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349602934&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2009.09.019

DO - 10.1016/j.febslet.2009.09.019

M3 - Article

C2 - 19755121

AN - SCOPUS:70349602934

SN - 0014-5793

VL - 583

SP - 3140

EP - 3144

JO - FEBS Letters

JF - FEBS Letters

IS - 19

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this