c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP

Su Yan Wang, Mihail Iordanov, Qinghong Zhang

    Research output: Contribution to journalArticlepeer-review

    44 Scopus citations


    Genetic knock out of the transcriptional co-repressor carboxyl-terminal- binding protein (CtBP) in mouse embryonic fibroblasts results in up-regulation of several genes involved in apoptosis. We predicted, therefore, that a propensity toward apoptosis might be regulated through changes in cellular CtBP levels. Previously, we have identified the homeodomain-interacting protein kinase 2 as such a regulator and demonstrated that HIPK2 activation causes Ser-422 phosphorylation and degradation of CtBP. In this study, we found that c-Jun NH2-terminal kinase 1 activation triggered CtBP phosphorylation on Ser-422 and subsequent degradation, inducing p53-independent apoptosis in human lung cancer cells. JNK1 has previously been linked to UV-directed apoptosis. Expression of MKK7-JNK1 or exposure to UV irradiation reduced cellular levels of CtBP via a proteasome-mediated pathway. This effect was prevented by JNK1 deficiency. In addition, sustained activation of the JNK1 pathway by cisplatin similarly triggered CtBP degradation. These findings provide a novel target for chemotherapy in cancers lacking p53.

    Original languageEnglish (US)
    Pages (from-to)34810-34815
    Number of pages6
    JournalJournal of Biological Chemistry
    Issue number46
    StatePublished - Nov 17 2006

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology


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