| First Author | Lolkema MP | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 23 | Pages | 22205-11 |
| PubMed ID | 15824109 | Mgi Jnum | J:101143 |
| Mgi Id | MGI:3590641 | Doi | 10.1074/jbc.M503220200 |
| Citation | Lolkema MP, et al. (2005) Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domain. J Biol Chem 280(23):22205-11 |
| abstractText | The tumor suppressor function of the von Hippel-Lindau protein (pVHL) has previously been linked to its role in regulating hypoxia-inducible factor levels. However, VHL gene mutations suggest a hypoxia-inducible factor-independent function for the N-terminal acidic domain in tumor suppression. Here, we report that phosphorylation of the N-terminal acidic domain of pVHL by casein kinase-2 is essential for its tumor suppressor function. This post-translational modification did not affect the levels of hypoxia-inducible factor; however, it did change the binding of pVHL to another known binding partner, fibronectin. Cells expressing phospho-defective mutants caused improper fibronectin matrix deposition and demonstrated retarded tumor formation in mice. We propose that phosphorylation of the acidic domain plays a role in the regulation of proper fibronectin matrix deposition and that this may be relevant for the development of VHL-associated malignancies. |
