PP2B-mediated dephosphorylation of c-Jun C terminus regulates phorbol ester-induced c-Jun/Sp1 interaction in A431 cells

Ben Kuen Chen, Chi Chen Huang, Wei Chiao Chang, Yun Ju Chen, Ushio Kikkawa, Ken Ichi Nakahama, Ikuo Morita, Wen Chang Chang

Research output: Contribution to journalArticle

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Abstract

The c-Jun/Sp1 interaction is essential for growth factor- and phorbol 12-myristate 13-acetate (PMA)-induced genes expression, including human 12(S)-lipoxygenase, keratin 16, cytosolic phospholipase A2, p21 WAF1/CIP1, and neuronal nicotinic acetylcholine receptor β4. Here, we examined the mechanism underlying the PMA-induced regulation on the interaction between c-Jun and Sp1. We found that treatment of cells with PMA induced a dephosphorylation at the C terminus of c-Jun at Ser-243 and a concomitant inhibition of PP2B by using PP2B small interfering RNA, resulting in reduction of PMA-induced gene expression as well as the c-Jun/Sp1 interaction. The c-Jun mutant TAM-67-3A, which contains three substitute alanines at Thr-231, Ser-243, and Ser-249 compared with TAM-67, binds more efficaciously with Sp1 and is about twice as efficacious as TAM-67 in inhibiting the PMA-induced activation of the 12(S)-lipoxygenase promoter. Importantly, PP2B not only dephosphorylates the c-Jun at Ser-243 but also interacts with c-Jun in PMA-treated cells. PMA stimulates the association of the PP2B/c-Jun/Sp1 complex with the promoter. These findings indicate the dephosphorylation of c-Jun C terminus is required for the c-Jun/Sp1 interaction and reveal that PP2B plays an important role in regulating c-Jun/Sp1 interaction in PMA-induced gene expression.

Original languageEnglish
Pages (from-to)1118-1127
Number of pages10
JournalMolecular Biology of the Cell
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Fingerprint

Phorbol Esters
Acetates
Arachidonate 12-Lipoxygenase
Gene Expression
Keratin-16
Cytosolic Phospholipases A2
phorbol-12-myristate
Nicotinic Receptors
Alanine
Small Interfering RNA
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

PP2B-mediated dephosphorylation of c-Jun C terminus regulates phorbol ester-induced c-Jun/Sp1 interaction in A431 cells. / Chen, Ben Kuen; Huang, Chi Chen; Chang, Wei Chiao; Chen, Yun Ju; Kikkawa, Ushio; Nakahama, Ken Ichi; Morita, Ikuo; Chang, Wen Chang.

In: Molecular Biology of the Cell, Vol. 18, No. 3, 03.2007, p. 1118-1127.

Research output: Contribution to journalArticle

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abstract = "The c-Jun/Sp1 interaction is essential for growth factor- and phorbol 12-myristate 13-acetate (PMA)-induced genes expression, including human 12(S)-lipoxygenase, keratin 16, cytosolic phospholipase A2, p21 WAF1/CIP1, and neuronal nicotinic acetylcholine receptor β4. Here, we examined the mechanism underlying the PMA-induced regulation on the interaction between c-Jun and Sp1. We found that treatment of cells with PMA induced a dephosphorylation at the C terminus of c-Jun at Ser-243 and a concomitant inhibition of PP2B by using PP2B small interfering RNA, resulting in reduction of PMA-induced gene expression as well as the c-Jun/Sp1 interaction. The c-Jun mutant TAM-67-3A, which contains three substitute alanines at Thr-231, Ser-243, and Ser-249 compared with TAM-67, binds more efficaciously with Sp1 and is about twice as efficacious as TAM-67 in inhibiting the PMA-induced activation of the 12(S)-lipoxygenase promoter. Importantly, PP2B not only dephosphorylates the c-Jun at Ser-243 but also interacts with c-Jun in PMA-treated cells. PMA stimulates the association of the PP2B/c-Jun/Sp1 complex with the promoter. These findings indicate the dephosphorylation of c-Jun C terminus is required for the c-Jun/Sp1 interaction and reveal that PP2B plays an important role in regulating c-Jun/Sp1 interaction in PMA-induced gene expression.",
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