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 journalArticle

39 Citations (Scopus)

Abstract

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
Volume281
Issue number46
DOIs
StatePublished - Nov 17 2006

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Co-Repressor Proteins
JNK Mitogen-Activated Protein Kinases
Carrier Proteins
Apoptosis
Phosphorylation
Chemical activation
Degradation
Homeodomain Proteins
Chemotherapy
Proteasome Endopeptidase Complex
Fibroblasts
Protein Kinases
Cisplatin
Proteolysis
Lung Neoplasms
Up-Regulation
Genes
Cells
Irradiation
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry

Cite this

c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP. / Wang, Su Yan; Iordanov, Mihail; Zhang, Qinghong.

In: Journal of Biological Chemistry, Vol. 281, No. 46, 17.11.2006, p. 34810-34815.

Research output: Contribution to journalArticle

Wang, Su Yan ; Iordanov, Mihail ; Zhang, Qinghong. / c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 46. pp. 34810-34815.
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