PMID- 15378003
OWN - NLM
STAT- MEDLINE
DCOM- 20041206
LR  - 20171116
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 23
IP  - 50
DP  - 2004 Oct 28
TI  - A new role for the Kruppel-like transcription factor KLF6 as an inhibitor of 
      c-Jun proto-oncoprotein function.
PG  - 8196-205
AB  - 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.
FAU - Slavin, Daniela A
AU  - Slavin DA
AD  - Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI - CONICET). 
      Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad 
      Nacional de Cordoba, Cordoba, Argentina.
FAU - Koritschoner, Nicolas P
AU  - Koritschoner NP
FAU - Prieto, Claudio C
AU  - Prieto CC
FAU - Lopez-Diaz, Fernando J
AU  - Lopez-Diaz FJ
FAU - Chatton, Bruno
AU  - Chatton B
FAU - Bocco, Jose Luis
AU  - Bocco JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (KLF6 protein, human)
RN  - 0 (Kruppel-Like Factor 6)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Cell Division/physiology
MH  - Cell Nucleus/metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Jurkat Cells
MH  - Kruppel-Like Factor 6
MH  - Kruppel-Like Transcription Factors
MH  - Phosphorylation
MH  - Protein Transport
MH  - Proto-Oncogene Proteins/metabolism/*physiology
MH  - Proto-Oncogene Proteins c-jun/*antagonists & inhibitors/metabolism/physiology
MH  - Trans-Activators/metabolism/*physiology
MH  - Transcription, Genetic/physiology
EDAT- 2004/09/21 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/09/21 05:00
PHST- 2004/09/21 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/09/21 05:00 [entrez]
AID - 1208020 [pii]
AID - 10.1038/sj.onc.1208020 [doi]
PST - ppublish
SO  - Oncogene. 2004 Oct 28;23(50):8196-205. doi: 10.1038/sj.onc.1208020.