A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-κB or ODC transactivation

Yang, Hsin-Sheng; Jansen, Aaron P; Nair, Rajalakshmi; Shibahara, Keiichi; Verma, Ajit K; Cmarik, Joan L; Colburn, Nancy H

doi:10.1038/sj.onc.1204137

Cited by 186Mechanisms of cancer metastasisCancer-related Molecular PathwaysSignaling Pathways in Disease

A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-κB or ODC transactivation

Yang, Hsin-Sheng, Jansen, Aaron P, Nair, Rajalakshmi, Shibahara, Keiichi, Verma, Ajit K, Cmarik, Joan L, Colburn, Nancy H·2001·Oncogene

DOI 10.1038/sj.onc.1204137

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Abstract

Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression of Pdcd4 protein is sufficient to suppress neoplastic transformation. To determine whether Pdcd4 suppresses neoplastic transformation through inhibiting known transformation required events, we examined the possibility that pdcd4 inhibited the activation of AP-1 or NF-kappaB dependent transcription or of ornithine decarboxylase (ODC) activity. Activation of AP-1-dependent transcriptional activity was inhibited by pdcd4 expression in a concentration dependent manner. In contrast, Pdcd4 slightly increased NF-kappaB-dependent transcription and did not alter ODC enzymatic activity. Previous studies suggested that activation of AP-1 was required for P+ cell transformation as well as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a transformation suppressor, possibly through inhibiting AP-1 activation in combination with other factors such as enhancing NF-kappaB activation. Pdcd4 may thus constitute a useful molecular target for cancer prevention.

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PDCD4 does not inhibit NF-κB in mouse JB6 cells where it inhibits AP-1 transactivation and transformation.
“PDCD4 does not inhibit NF-κB in mouse JB6 cells where it inhibits AP-1 transactivation and transformation (26).”
From Tumor suppressor PDCD4 inhibits NF-κB-dependent transcription in human glioblastoma cells by direct interaction with p65 (2014) · cites this paper as [26]

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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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Abstract 3096: c-Myc regulates MAP4K1 expression and AP-1 activity in Pdcd4 knock-down cells
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Authors: Yang, H.-S., Jansen, A. P., Nair, R., Shibahara, K., Verma, A. K., Cmarik, J. L., & Colburn, N. H.
Affiliations: Frederick National Laboratory for Cancer Research (US)
University of Wisconsin–Madison (US)
Kyoto University (JP)
ORCID: Yang, Hsin-Sheng
Verma, Ajit K
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2001-02-08
Volume: 20
Issue: 6
Pages: 669-676
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1204137
OpenAlex: W2093224647
Cited by: 185
References: 38
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 7 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 7 · 2014: 17 · 2013: 17 · 2012: 12
FWCI: 2.77
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: PDCD4, AP-1 transactivation, NF-κB, ornithine decarboxylase, JB6 epidermal cells, transcriptional regulation, cancer prevention, tumor suppressor
MeSH terms: Animals, Cell Transformation, Neoplastic, Ornithine Decarboxylase, Proteins, Tetradecanoylphorbol Acetate, Transcriptional Activation, Genes, Tumor Suppressor, NF-kappa B, RNA-Binding Proteins, Transcription Factor AP-1, Apoptosis Regulatory Proteins, Mice

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A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-κB or ODC transactivation

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