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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
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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“PDCD4 was shown to inhibit the activation of c-Jun by suppressing the JNK-activation in avian QT6 cells [34] and to suppress the expression of the upstream kinase MAP4K1 in RKO human colon carcinoma cells [33].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [34]
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Metadata
- Authors
- Bitomsky, N., Böhm, M., & Klempnauer, K.-H.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Klempnauer, Karl-Heinz
- Venue
- Oncogene
- Published
- 2004-08-30
- Volume
- 23
- Issue
- 45
- Pages
- 7484-7493
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- 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
- 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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