| First Author | Frew IJ | Year | 2013 |
| Journal | Eur J Cancer | Volume | 49 |
| Issue | 10 | Pages | 2433-40 |
| PubMed ID | 23541568 | Mgi Jnum | J:198361 |
| Mgi Id | MGI:5496467 | Doi | 10.1016/j.ejca.2013.02.024 |
| Citation | Frew IJ, et al. (2013) Genetic deletion of the long isoform of the von Hippel-Lindau tumour suppressor gene product alters microtubule dynamics. Eur J Cancer 49(10):2433-40 |
| abstractText | The von Hippel-Lindau tumour suppressor protein (pVHL) controls distinct cellular responses ranging from targeting hypoxia inducible factor alpha (HIFalpha) subunits for degradation and promotion of chromosomal stability to the regulation of microtubule dynamics. pVHL is produced in mammalian cells as a long and a short isoform, derived from alternate translational initiation sites in a single Vhl mRNA. However, it is unclear whether these isoforms have different cell biological activities that may represent different tumour suppressor activities of pVHL. Through a knock-in strategy to mutate the first translational initiation site from methionine to leucine (M1L) we have genetically deleted the pVHL long protein isoform in mice, allowing dissection of isoform-specific functions of pVHL. Vhl(M1L/M1L) mice exhibit no obvious phenotypic abnormalities. While numerous pVHL-mediated activities, including degradation of HIFalpha transcription factors, are unaffected, microtubule dynamics are altered in primary cells derived from Vhl(M1L/M1L) mice to an extent similar to that seen following complete loss of pVHL function. We conclude that the microtubule-regulating function and the HIFalpha-regulating function of pVHL are separable activities mediated by different protein isoforms. |
