title: A new role for the Kruppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function.
abstract: Kruppel-like transcription factors (KLFs) represent one of the most diverse set of regulators in vertebrate organisms. KLF family members are involved in cell proliferation and differentiation control in normal as well as in pathological situations. Here, we demonstrate that KLF6 behaves as a functional antagonist of the c-Jun proto-oncoprotein. Thus, KLF6 overexpression downregulated c-Jun-dependent transcription and a physical interaction between c-Jun and KLF6 was detected. Moreover, cell proliferation induced by c-Jun was significantly decreased by KLF6. The inhibition of c-Jun functions correlates directly with c-Jun protein degradation induced by KLF6. We also show that all KLF6 effects on c-Jun were largely dependent on phorbol ester (TPA/ionomycin) extracellular stimulation, which enhanced KLF6 nuclear translocation and transcriptional activity and modified its phosphorylation status. Our data are consistent with a novel mechanism of KLF6's role as an inhibitor of cell proliferation by counteracting the function of the c-Jun proto-oncoprotein involving enhanced c-Jun degradation by the proteasome-dependent pathway, and further reinforces KLF6 as a potential tumor suppressor gene product.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI - CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Slavin
authors.forename: Nicolás P
authors.initials: NP
authors.lastname: Koritschoner
authors.forename: Claudio C
authors.initials: CC
authors.lastname: Prieto
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: López-Díaz
authors.forename: Bruno
authors.initials: B
authors.lastname: Chatton
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bocco
mesh_terms: D000818:Animals; D019556:COS Cells; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D019169:Jurkat Cells; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D010766:Phosphorylation; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators