Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation
Abstract
Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5'-untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-myb mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-myb mRNA by Pdcd4 is dependent on sequences located within the c-myb-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-myb RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-myb mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.
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PDCD4 protein interacts with the coding region of c-Myb and A-Myb mRNA through the RNA binding domain and inhibits translation of the mRNA.
“It was shown that PDCD4-protein interacts with the coding region of c-Myb and A-Myb mRNA through the RNA binding domain and inhibits the translation of the mRNA [28,29].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [28]
PDCD4 regulates translation of two transcription factors, namely p53 and c-myb.
“PDCD4 regulates translation of two transcription factors, namely p53 and c-myb (20,21).”
From Tumor suppressor PDCD4 inhibits NF-κB-dependent transcription in human glioblastoma cells by direct interaction with p65 (2014) · cites this paper as [20]
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References 43 · Cited by 50
- Authors
- Singh, P., Wedeken, L., Waters, L. C., Carr, M. D., & Klempnauer, K.-H.
- Affiliations
- University of Münster (DE)
- University of Leicester (GB)
- Corresponding author
- Klempnauer, K-H
- Venue
- Oncogene
- Published
- 2011-06-06
- Volume
- 30
- Issue
- 49
- Pages
- 4864-4873
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2041824736
- Cited by
- 50
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 8 · 2013: 4 · 2012: 3
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Funders
- Wellcome Trust
- 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 › RNA and protein synthesis mechanisms
- Keywords
- PDCD4, protein synthesis inhibition, mRNA translation, RNA-binding proteins, tumor suppressor, N-terminal domain, mRNA binding, coding sequences, RNA-binding domain
- MeSH terms
- Animals, Cell Line, Chickens, Humans, Protein Binding, RNA, Messenger, Substrate Specificity, Protein Biosynthesis, Open Reading Frames, RNA-Binding Proteins, Protein Structure, Tertiary, Response Elements, Proto-Oncogene Proteins c-myb, Apoptosis Regulatory Proteins
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