The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA
Abstract
The Pdcd4 gene has originally been isolated in a search for genes that are activated in cells undergoing apoptosis. Independent of these studies, the Pdcd4 gene has been implicated in the suppression of tumor-promoter-mediated transformation of keratinocytes and as a downstream target of Myb in hematopoietic cells. The Pdcd4 protein has weak homology to the eucaryotic translation initiation factor eIF4G and has been shown to interact with certain translation initiation factors. To explore the molecular function of the Pdcd4 protein, we have studied its subcellular localization. We show that the Pdcd4 protein is a predominantly nuclear protein under normal growth conditions and that it is exported from the nucleus by a leptomycin B-sensitive mechanism upon serum withdrawal. The protein contains two nuclear export signals, one of which is very potent. In addition, we demonstrate that the Pdcd4 protein has RNA-binding activity and that the sequences involved in RNA-binding are located in the amino-terminal part of the protein. Taken together, our data raise the possibility that Pdcd4 is involved in some aspect of nuclear RNA metabolism in addition to its suspected role in protein translation.
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PDCD4 protein contains one RNA binding site at the N-terminal region.
“PDCD4-protein contains one RNA binding site at the N-terminal region [27] (Figure 2) and inhibits some protein elongation binding to special secondary RNA structures in the coding region of the mRNA (Figure 3).”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [27]
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- Authors
- Böhm, M., Sawicka, K., Siebrasse, J. P., Brehmer-Fastnacht, A., Peters, R., & Klempnauer, K.-H.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Klempnauer, Karl-Heinz
- Venue
- Oncogene
- Published
- 2003-07-31
- Volume
- 22
- Issue
- 31
- Pages
- 4905-4910
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1966417898
- Cited by
- 101
- References
- 28
- Citations by year
- 2026: 1 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 9
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds der Chemischen Industrie
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- PDCD4, nuclear export, nucleocytoplasmic shuttling, nuclear export signal, RNA binding, subcellular localization, leptomycin B, apoptosis, translation initiation factors, tumor suppressor, keratinocyte transformation, MYB
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cell Nucleus, Cells, Cultured, Chickens, Clone Cells, Cytoplasm, Enzyme Inhibitors, Fatty Acids, Unsaturated, Fibroblasts, Microinjections, Molecular Sequence Data, Protein Kinase C, RNA, Transfection, 3T3 Cells, RNA-Binding Proteins, Culture Media, Serum-Free, Apoptosis, Protein Transport, Apoptosis Regulatory Proteins, Mice
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