Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

C. C. Huang, J. M. Wang, U. Kikkawa, H. Mukai, M. R. Shen, I. Morita, B. K. Chen, W. C. Chang

研究成果: 雜誌貢獻文章

20 引文 (Scopus)

摘要

The proto-oncogene c-Jun plays an important role in regulating tumor progression. We previously reported that the serine/threonine phosphatase calcineurin (CaN, also called PP2B) dephosphorylates the C-terminus (Ser-243) of c-Jun, resulting in the increase in c-Jun and Sp1 interaction, and subsequent c-Jun-induced gene expression. Here, we demonstrate the interaction of c-Jun and CaN in the nucleus of living cells by fluorescence resonance energy transfer assay and that this interaction is mediated through the calmodulin-binding domain of CaN. Furthermore, c-Jun protein stability was altered by CaN-mediated dephosphorylation at the Ser-243 site of c-Jun. The half-life of the c-Jun mutant, c-Jun-S243A was longer than that of the wild-type c-Jun. Moreover, silencing of endogenous CaN expression led to increased c-Jun ubiquitination and decreased stability. In 46% of clinical cervical tissue samples obtained from patients with cervical cancer, enhanced c-Jun and CaN expression, as well as decreased phospho-Ser-243 expression levels were detected. Our results suggest that CaN stabilizes c-Jun by dephosphorylating c-Jun at Ser-243 to enhance its tumorigenic ability.

原文英語
頁(從 - 到)2422-2429
頁數8
期刊Oncogene
27
發行號17
DOIs
出版狀態已發佈 - 四月 10 2008
對外發佈Yes

指紋

Proto-Oncogene Proteins c-jun
jun Genes
Protein Stability
Calcineurin
Fluorescence Resonance Energy Transfer
Phosphoprotein Phosphatases
Ubiquitination
Calmodulin
Cell Nucleus
Uterine Cervical Neoplasms
Half-Life
Gene Expression
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

引用此文

Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation. / Huang, C. C.; Wang, J. M.; Kikkawa, U.; Mukai, H.; Shen, M. R.; Morita, I.; Chen, B. K.; Chang, W. C.

於: Oncogene, 卷 27, 編號 17, 10.04.2008, p. 2422-2429.

研究成果: 雜誌貢獻文章

Huang, C. C. ; Wang, J. M. ; Kikkawa, U. ; Mukai, H. ; Shen, M. R. ; Morita, I. ; Chen, B. K. ; Chang, W. C. / Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation. 於: Oncogene. 2008 ; 卷 27, 編號 17. 頁 2422-2429.
@article{a73cc768dbca4441b898b670d6e2d499,
title = "Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation",
abstract = "The proto-oncogene c-Jun plays an important role in regulating tumor progression. We previously reported that the serine/threonine phosphatase calcineurin (CaN, also called PP2B) dephosphorylates the C-terminus (Ser-243) of c-Jun, resulting in the increase in c-Jun and Sp1 interaction, and subsequent c-Jun-induced gene expression. Here, we demonstrate the interaction of c-Jun and CaN in the nucleus of living cells by fluorescence resonance energy transfer assay and that this interaction is mediated through the calmodulin-binding domain of CaN. Furthermore, c-Jun protein stability was altered by CaN-mediated dephosphorylation at the Ser-243 site of c-Jun. The half-life of the c-Jun mutant, c-Jun-S243A was longer than that of the wild-type c-Jun. Moreover, silencing of endogenous CaN expression led to increased c-Jun ubiquitination and decreased stability. In 46{\%} of clinical cervical tissue samples obtained from patients with cervical cancer, enhanced c-Jun and CaN expression, as well as decreased phospho-Ser-243 expression levels were detected. Our results suggest that CaN stabilizes c-Jun by dephosphorylating c-Jun at Ser-243 to enhance its tumorigenic ability.",
keywords = "c-jun, Calcineurin, Cell transformation, Dephosphorylation",
author = "Huang, {C. C.} and Wang, {J. M.} and U. Kikkawa and H. Mukai and Shen, {M. R.} and I. Morita and Chen, {B. K.} and Chang, {W. C.}",
year = "2008",
month = "4",
day = "10",
doi = "10.1038/sj.onc.1210888",
language = "English",
volume = "27",
pages = "2422--2429",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "17",

}

TY - JOUR

T1 - Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

AU - Huang, C. C.

AU - Wang, J. M.

AU - Kikkawa, U.

AU - Mukai, H.

AU - Shen, M. R.

AU - Morita, I.

AU - Chen, B. K.

AU - Chang, W. C.

PY - 2008/4/10

Y1 - 2008/4/10

N2 - The proto-oncogene c-Jun plays an important role in regulating tumor progression. We previously reported that the serine/threonine phosphatase calcineurin (CaN, also called PP2B) dephosphorylates the C-terminus (Ser-243) of c-Jun, resulting in the increase in c-Jun and Sp1 interaction, and subsequent c-Jun-induced gene expression. Here, we demonstrate the interaction of c-Jun and CaN in the nucleus of living cells by fluorescence resonance energy transfer assay and that this interaction is mediated through the calmodulin-binding domain of CaN. Furthermore, c-Jun protein stability was altered by CaN-mediated dephosphorylation at the Ser-243 site of c-Jun. The half-life of the c-Jun mutant, c-Jun-S243A was longer than that of the wild-type c-Jun. Moreover, silencing of endogenous CaN expression led to increased c-Jun ubiquitination and decreased stability. In 46% of clinical cervical tissue samples obtained from patients with cervical cancer, enhanced c-Jun and CaN expression, as well as decreased phospho-Ser-243 expression levels were detected. Our results suggest that CaN stabilizes c-Jun by dephosphorylating c-Jun at Ser-243 to enhance its tumorigenic ability.

AB - The proto-oncogene c-Jun plays an important role in regulating tumor progression. We previously reported that the serine/threonine phosphatase calcineurin (CaN, also called PP2B) dephosphorylates the C-terminus (Ser-243) of c-Jun, resulting in the increase in c-Jun and Sp1 interaction, and subsequent c-Jun-induced gene expression. Here, we demonstrate the interaction of c-Jun and CaN in the nucleus of living cells by fluorescence resonance energy transfer assay and that this interaction is mediated through the calmodulin-binding domain of CaN. Furthermore, c-Jun protein stability was altered by CaN-mediated dephosphorylation at the Ser-243 site of c-Jun. The half-life of the c-Jun mutant, c-Jun-S243A was longer than that of the wild-type c-Jun. Moreover, silencing of endogenous CaN expression led to increased c-Jun ubiquitination and decreased stability. In 46% of clinical cervical tissue samples obtained from patients with cervical cancer, enhanced c-Jun and CaN expression, as well as decreased phospho-Ser-243 expression levels were detected. Our results suggest that CaN stabilizes c-Jun by dephosphorylating c-Jun at Ser-243 to enhance its tumorigenic ability.

KW - c-jun

KW - Calcineurin

KW - Cell transformation

KW - Dephosphorylation

UR - http://www.scopus.com/inward/record.url?scp=42049106500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42049106500&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1210888

DO - 10.1038/sj.onc.1210888

M3 - Article

C2 - 17952113

AN - SCOPUS:42049106500

VL - 27

SP - 2422

EP - 2429

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 17

ER -