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  • Original Paper
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A new role for the Krüppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function

Oncogene volume 23, pages 8196–8205 (2004)Cite this article

Abstract

Krüppel-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.

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Acknowledgements

We are grateful to L Patrito for his continuous encouragement and support, to C Kedinger for many helpful discussions and D Perez for reagents and critical reading of the manuscript. We also thank H Luján and C Alvarez for their generous advice on immunofluorescence microscopy, and D Donoghue for his help on proliferation assays. This work was supported by grants from Secretaría de Ciencia y Tecnología – Universidad Nacional de Córdoba (SECyT-UNC); Agencia Nacional de Promoción Científica y Tecnológica – Argentina, Agencia Córdoba Ciencia, Consejo Nacional de Investigaciones y Tecnológicas (CONICET), Ministerio de Salud (Becas Ramón Carrillo – Arturo Oñativia to NPK and JLB) and in part by Fundación Antorchas and Third World Academy of Sciences to NPK. DAS and FL-D are recipients of CONICET fellowships. CCP was a recipient of FOMEC fellowship. NPK and JLB are Investigators of CONICET.

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  1. Claudio C Prieto

    Present address: Laboratorio de Cultivos Celulares. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

Authors and Affiliations

  1. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina

    Daniela A Slavin, Nicolás P Koritschoner, Claudio C Prieto, Fernando J López-Díaz & José Luis Bocco

  2. Ecole Supérieure de Biotechnologie de Strasbourg, Université Louis Pasteur, Strasbourg Illkirch, France

    Bruno Chatton

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  1. Daniela A Slavin
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Correspondence to José Luis Bocco.

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Slavin, D., Koritschoner, N., Prieto, C. et al. A new role for the Krüppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function. Oncogene 23, 8196–8205 (2004). https://doi.org/10.1038/sj.onc.1208020

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