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Updated: Jun 1, 2026

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation
P Singh1, L Wedeken, L C Waters
1Institute for Biochemistry, Westfälische-Wilhelms-Universität Münster, Münster, Germany.
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.
Insights
Programmed cell death protein 4 (Pdcd4) directly suppresses translation of c-myb mRNA. Its N-terminal domain targets Pdcd4 to specific RNA sequences, revealing a novel mechanism in gene regulation.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Programmed cell death protein 4 (Pdcd4) is a tumor suppressor involved in transcription and translation.
- Pdcd4's cytoplasmic role in suppressing translation of structured mRNAs is known, but target mRNAs and recruitment mechanisms remain unclear.
Purpose of the Study:
- To identify the first natural messenger RNA (mRNA) target of Pdcd4.
- To elucidate the mechanisms by which Pdcd4 targets specific mRNAs for translational suppression.
Main Methods:
- Identification of c-myb mRNA as a Pdcd4 target.
- Analysis of Pdcd4's translational suppression of c-myb mRNA.
- Investigation of the role of Pdcd4's N-terminal domain in RNA binding and targeting.
Main Results:
- c-myb mRNA is identified as the first natural translational target of Pdcd4.
- Pdcd4-mediated translational suppression of c-myb mRNA depends on coding region sequences.
- Pdcd4's N-terminal domain is crucial for targeting Pdcd4 to c-myb RNA via preferential binding.
Conclusions:
- Pdcd4 directly suppresses the translation of a natural mRNA (c-myb).
- The N-terminal domain of Pdcd4 plays a key role in targeting it to specific mRNAs.
- This study reveals a novel mechanism for Pdcd4-mediated gene regulation at the translational level.
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