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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | O'brate, Aurora Giannakakou, Paraskevi Carbonaro, Marisa |
| Description | Author Affiliation: Carbonaro M ( Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY 10065, USA.) |
| Abstract | The hypoxia inducible factor 1α (HIF-1α) is overexpressed in solid tumors, driving tumor angiogenesis and survival. However, the mechanisms regulating HIF-1α expression in solid tumors are not fully understood. In this study, we find that microtubule integrity and dynamics are intricately involved in orchestrating HIF-1α translation. HIF-1α messenger RNA (mRNA) traffics on dynamic microtubules when it is actively translated. Microtubule perturbation by taxol (TX) and other microtubule-targeting drugs stalls HIF-1α mRNA transport and releases it from polysomes, suppressing its translation. Immunoprecipitation of the P-body component Argonaute 2 (Ago2) after microtubule disruption shows significant enrichment of HIF-1α mRNAs and HIF-targeting microRNAs (miRNAs). Inhibition of HIF-repressing miRNAs or Ago2 knockdown abrogates TX’s ability to suppress HIF-1α translation. Interestingly, microtubule repolymerization after nocodazole washout allows HIF-1α mRNA to reenter active translation, suggesting that microtubule dynamics exert tight yet reversible control over HIF-1α translation. Collectively, we provide evidence for a new mechanism of microtubule-dependent HIF-1α translation with important implications for cell biology. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 192 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2011-01-10 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cytoplasmic Structures Metabolism Hypoxia-Inducible Factor 1, Alpha Subunit Genetics Microtubules Protein Biosynthesis RNA Transport 3' Untranslated Regions Argonaute Proteins Chemical Precipitation Drug Effects Eukaryotic Initiation Factor-2 Green Fluorescent Proteins HeLa Cells Nocodazole Pharmacology Paclitaxel Polymerization Protein Binding RNA, Messenger Recombinant Fusion Proteins Tubulin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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