KLF6 Tumor Suppressor Engages c-Jun Oncoprotein in an Apoptotic Pathway through JNK2 Phosphorylation.

ANDREOLI VERÓNICA; PETITI JUAN PABLO; TRUCCO LUCAS; TORRES, ALICIA ; BOCCO, JOSÉ LUIS

Los Cocos - Córdoba

Simposio; First South American Spring Symposium in Signal Transduction and Molecular Medicine; 2010

NIDCR, NIH, Bethesda, MD, USA; University of Massachusetts, Worcester, MA, USA and University of Buenos Aires

Expression of the Krüppel-like Factor 6 (KLF6) is responsive to external cues mediated by several physical and chemical stimuli though the underlying mechanisms and how they are integrated with cell biology are largely undeciphered. According to the stimulus detected by the cell, KLF6 contributes to reprogram the transcriptional response and/or interact functionally with other transcription factors like c-Jun to organize the adaptive cell response (e.g. proliferation rate or apoptosis) in a coordinated fashion. Interestingly, after DNA damage signaling KLF6 promotes apoptosis involving sustained phosphorylation of c-Jun by JNK2. KLF6 expression improves JNK2 activity leading to a transient increase of c-Jun phosphorylation in cells lacking JNK1 activity, correlating with KLF6 nuclear translocation. In this particular context of jnk1-/ - cells, expression of KLF6 was directly associated with increased levels of p53 transcript, induction of p73 promoter, activation of caspases-3 /-7 and increased cellular labeling with Annexin-V. Additionally, experiments are consistent with the idea that KLF6 exploits the pro-apoptotic properties described for the hyper-phosphorylated form of the c-Jun oncoprotein which in turn is essential to promote the "switch" of p53 function from cell cycle arrest towards apoptosis.