Reference - Detail
| RRC ID | 74775 |
|---|---|
| Author | Pulianmackal AJ, Kanakousaki K, Flegel K, Grushko OG, Gourley E, Rozich E, Buttitta LA. |
| Title | Misregulation of Nucleoporins 98 and 96 leads to defects in protein synthesis that promote hallmarks of tumorigenesis. |
| Journal | Dis Model Mech |
| Abstract |
Nucleoporin 98KD (Nup98) is a promiscuous translocation partner in hematological malignancies. Most disease models of Nup98 translocations involve ectopic expression of the fusion protein under study, leaving the endogenous Nup98 loci unperturbed. Overlooked in these approaches is the loss of one copy of normal Nup98 in addition to the loss of Nup96 - a second Nucleoporin encoded within the same mRNA and reading frame as Nup98 - in translocations. Nup98 and Nup96 are also mutated in a number of other cancers, suggesting that their disruption is not limited to blood cancers. We found that reducing Nup98-96 function in Drosophila melanogaster (in which the Nup98-96 shared mRNA and reading frame is conserved) de-regulates the cell cycle. We found evidence of overproliferation in tissues with reduced Nup98-96, counteracted by elevated apoptosis and aberrant signaling associated with chronic wounding. Reducing Nup98-96 function led to defects in protein synthesis that triggered JNK signaling and contributed to hallmarks of tumorigenesis when apoptosis was inhibited. We suggest that partial loss of Nup98-96 function in translocations could de-regulate protein synthesis, leading to signaling that cooperates with other mutations to promote tumorigenesis. |
| Volume | 15(3) |
| Published | 2022-3-1 |
| DOI | 10.1242/dmm.049234 |
| PII | 274202 |
| PMID | 35107131 |
| PMC | PMC8938402 |
| MeSH | Animals Cell Transformation, Neoplastic Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Nuclear Pore Complex Proteins* / genetics RNA, Messenger |
| IF | 4.651 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 20 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | DGRC#109696 DGRC#109767 DGRC#109768 DGRC#115462 |