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 language | English |
|---|---|
| Pages (from-to) | 2422-2429 |
| Number of pages | 8 |
| Journal | Oncogene |
| Volume | 27 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - 2008 Apr 10 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Genetics
- Molecular Biology
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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 journal › Article
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 -