Cited by 134Cancer-related Molecular PathwaysProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

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Transformation suppressor protein Pdcd4 interferes with JNK-mediated phosphorylation of c-Jun and recruitment of the coactivator p300 by c-Jun

Bitomsky, Nadja, Böhm, Maret, Klempnauer, Karl-Heinz·2004·Oncogene

DOI 10.1038/sj.onc.1208064

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Abstract

The transformation suppressor gene Pdcd4 (programmed cell death gene 4) inhibits the tumor-promoter mediated transformation of mouse keratinocytes and has recently been implicated as a potential tumor suppressor gene in the development of human lung cancer. Biochemical analysis has suggested that the Pdcd4 protein is involved in protein translation as well as in nuclear events. Recent work has shown that Pdcd4 suppresses the transactivation of AP-1 responsive promoters by c-Jun, suggesting that the transformation-suppressor activity of Pdcd4 might be due, at least in part, to the inhibition of c-Jun activity. Here, we have addressed how Pdcd4 inhibits c-Jun. We show that Pdcd4 interferes with the phosphorylation of c-Jun by Jun N-terminal kinase (JNK). The inhibition of c-Jun phosphorylation by Pdcd4 appears not to be due to a general suppression of JNK activity, our data rather suggest that Pdcd4 interacts with c-Jun and thereby blocks phosphorylation of c-Jun. In addition to affecting c-Jun phosphorylation, Pdcd4 blocks the recruitment of the coactivator p300 by c-Jun. Taken together, our results strongly suggest that Pdcd4 is directly involved in the regulation of c-Jun activity.

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Authors: Bitomsky, N., Böhm, M., & Klempnauer, K.-H.
Affiliations: University of Münster (DE)
Corresponding author: Klempnauer, Karl-Heinz
ORCID: Klempnauer, Karl-Heinz
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2004-08-30
Volume: 23
Issue: 45
Pages: 7484-7493
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1208064
OpenAlex: W2081476178
Cited by: 134
References: 34
Citations by year: 2025: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 10 · 2015: 5 · 2014: 10 · 2013: 5 · 2012: 9
FWCI: 1.92
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Krebshilfe
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: PDCD4, c-Jun, JNK, c-Jun phosphorylation, P300, coactivator recruitment, AP-1 transactivation, tumor suppressor, keratinocyte transformation, lung cancer, protein-protein interaction
MeSH terms: Animals, Cell Line, Humans, Nuclear Proteins, Phosphorylation, Protein Binding, Quail, Trans-Activators, RNA-Binding Proteins, Proto-Oncogene Proteins c-jun, Mitogen-Activated Protein Kinase Kinases, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Apoptosis Regulatory Proteins

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Transformation suppressor protein Pdcd4 interferes with JNK-mediated phosphorylation of c-Jun and recruitment of the coactivator p300 by c-Jun

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