Mucha et al. 2022 (PRJNA805181)
General Details
| Title | Ribosome profiling of Murine Embryonic Fibroblasts in the context of different Fbxo4 and hnRNPK status. |
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| Organism | |
| Number of Samples | 8 |
| Release Date | 2022/02/10 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP359195 |
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| ENA | SRP359195 |
| GEO | GSE196483 |
| BioProject | PRJNA805181 |
Publication
| Title | |
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| Authors | Mucha B, Qie S, Bajpai S, Tarallo V, Diehl JN, Tedeschi F, Zhou G, Gao Z, Flashner S, Klein-Szanto AJ, Hibshoosh H, Masataka S, Chajewski OS, Majsterek I, Pytel D, Hatzoglou M, Der CJ, Nakagawa H, Bass AJ, Wong KK, Fuchs SY, Rustgi AK, Jankowsky E, Diehl JA |
| Journal | Nature communications |
| Publication Date | 2022 Nov 3 |
| Abstract | Heterogeneous Nuclear Ribonucleoprotein K (hnRNPK) is a multifunctional RNA binding protein (RBP) localized in the nucleus and the cytoplasm. Abnormal cytoplasmic enrichment observed in solid tumors often correlates with poor clinical outcome. The mechanism of cytoplasmic redistribution and ensuing functional role of cytoplasmic hnRNPK remain unclear. Here we demonstrate that the SCF Fbxo4 E3 ubiquitin ligase restricts the pro-oncogenic activity of hnRNPK via K63 linked polyubiquitylation, thus limiting its ability to bind target mRNA. We identify SCF Fbxo4 -hnRNPK responsive mRNAs whose products regulate cellular processes including proliferation, migration, and invasion. Loss of SCF Fbxo4 leads to enhanced cell invasion, migration, and tumor metastasis. C-Myc was identified as one target of SCF Fbxo4 -hnRNPK. Fbxo4 loss triggers hnRNPK-dependent increase in c-Myc translation, thereby contributing to tumorigenesis. Increased c-Myc positions SCF Fbxo4 -hnRNPK dysregulated cancers for potential therapeutic interventions that target c-Myc-dependence. This work demonstrates an essential role for limiting cytoplasmic hnRNPK function in order to maintain translational and cellular homeostasis. © 2022. The Author(s). |
| PMC | PMC9633729 |
| PMID | 36329064 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR17971141 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 |  |
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| SRR17971140 | PRJNA805181 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR17971139 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 | |
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| SRR17971138 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 | |
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| SRR17971137 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 | |
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| SRR17971136 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 | |
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| SRR17971135 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 | |
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| SRR17971134 | PRJNA805181 | Mus musculus | Fibroblast | Ribo-Seq | 0.0 | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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