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

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16 Citations (Scopus)

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 - 2007 Mar 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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