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- Title
Kruppel-like factor 5 modulates p53-independent apoptosis through Pim1 survival kinase in cancer cells.
- Authors
Zhao, Y.; Hamza, M. S.; Leong, H. S.; Lim, C.-B.; Pan, Y.-F.; Cheung, E.; Soo, K.-C.; Iyer, N. G.
- Abstract
Although Kruppel-like factor 5 (KLF5) is a transcription factor that has been implicated in pathways critical to carcinogenesis, controversy persists as to whether it functions as a tumor suppressor or as an oncogene. Here, we describe a novel role for KLF5 in a p53-independent apoptotic pathway. Using RNA-interference technology, we show that cells deficient in KLF5 have increased sensitivity to DNA damage, regardless of p53 status. Both p53 and p53-dependent factors are unaffected by KLF5 depletion. Instead, the apoptotic phenotype consequent to damage is associated with reduced bad phosphorylation, and downregulation of Pim1. Consistently, transfection of wild-type Pim1 is sufficient to rescue this phenotype. Previous data have shown a number of putative Sp1-binding consensus sequences on the Pim1 promoter. Remarkably, chromatin immunoprecipitation studies show that KLF5 binds to the Pim1 promoter, and that binding increases soon after damage. These results identify a novel, p53-independent apoptotic pathway through which KLF5 functions in response to DNA damage. Therapeutic deregulation of this pathway could be used to modulate chemosensitivity.Oncogene (2008) 27, 1–8; doi:10.1038/sj.onc.1210625; published online 2 July 2007
- Subjects
TRANSCRIPTION factors; PROTEINS; CARCINOGENESIS; APOPTOSIS; TUMOR growth
- Publication
Oncogene, 2008, Vol 27, Issue 1, p1
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210625