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

C. C. Huang, Ju-Ming Wang, U. Kikkawa, H. Mukai, Meng-Ru Shen, I. Morita, Ben-Kuen Chen, W. C. Chang

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2422-2429
Number of pages8
JournalOncogene
Volume27
Issue number17
DOIs
Publication statusPublished - 2008 Apr 10

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

@article{c3c45807518e4de0927af75c932e44ce,
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.",
author = "Huang, {C. C.} and Ju-Ming Wang and U. Kikkawa and H. Mukai and Meng-Ru Shen and I. Morita and Ben-Kuen Chen 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",

}

Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation. / Huang, C. C.; Wang, Ju-Ming; Kikkawa, U.; Mukai, H.; Shen, Meng-Ru; Morita, I.; Chen, Ben-Kuen; Chang, W. C.

In: Oncogene, Vol. 27, No. 17, 10.04.2008, p. 2422-2429.

Research output: Contribution to journalArticle

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, Ju-Ming

AU - Kikkawa, U.

AU - Mukai, H.

AU - Shen, Meng-Ru

AU - Morita, I.

AU - Chen, Ben-Kuen

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.

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 -