THE TRANSCRIPTION FACTOR KLF6 IS REGULATED BY JNK AND P38 PATHWAYS

ANDREOLI V.; KORITSCHONER N.; CHATTON B.; BOCCO J.L.

Mar del Plata-Argentina

Congreso; 43th Reunión Anual. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

KLF6 is a potential tumor suppressor whose expression is responsive to growth factors, DNA-damage and infections. This factor interacts with the c-Jun oncoprotein and induces its degradation leading to inhibition of cell proliferation. MAPkinases are main regulators of the c-Jun activity and stability. However, the biochemical response to extracellular stimuli and its effects in c-Junsustained proliferation are still unknown. We observed that KLF6 protein levels were markedly reduced in cells upon expression of JNKs. Moreover, JNK2 activity was associated to KLF6 translocation from the cytoplasm to the nucleus. Additionally, activated p38 isoforms also decreased KLF6 protein levels. Interestingly, KLF6 was phosphorylated in vivo in cells under minimal ERK and p38 activities, indicating a constitutive KLF6 phosphorylation independently of MAPKs. These results show that JNK and p38 pathways are mainly involved in the regulation of protein stability and cell localization of KLF6. Thus, increased activity of JNK1 and p38 diminished KLF6 protein levels whereas allowed high stability and activation of c-Jun. Conversely, JNK2 substantially increased KLF6 targeting to the nucleus whereas c-Jun activity was low, suggesting that activated c- Jun and KLF6 are mutually exclusive, correlating with enhanced or reduced cell proliferation rate, respectively.