CUP Faculty Research
Document Type
Article
Publication Date
11-1-2006
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.
Published In
The Journal of Biological Chemistry
Recommended Citation
Wang, Su-Yan; Iordanov, Mihail; and Zhang, Qinghong, "c-Jun NH2-terminal Kinase Promotes Apoptosis by Down-Regulating the Transcriptional Co-repressor CtBP" (2006). CUP Faculty Research. 116.
https://digitalcommons.csp.edu/cup_commons_faculty/116
Source
CU Commons -- Math and Science Department Faculty Research
Comments
Publication Information.
Wang, S.-Y., Iordanov, M., & Zhang, Q. (2006). c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP. The Journal of Biological Chemistry, 281(46), 34810-34815. doi:10.1074/jbc.M607484200
doi:10.1074/jbc.M607484200