The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
pVHL Modification by NEDD8 Is Required for Fibronectin Matrix Assembly and Suppression of Tumor Development
Open accessAbstract
Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is the cause of the familial VHL disease and most sporadic renal clear-cell carcinomas (RCC). pVHL has been shown to play a role in the destruction of hypoxia-inducible factor alpha (HIF-alpha) subunits via ubiquitin-mediated proteolysis and in the regulation of fibronectin matrix assembly. Although most disease-causing pVHL mutations hinder the regulation of the HIF pathway, every disease-causing pVHL mutant tested to date has failed to promote the assembly of the fibronectin matrix, underscoring its potential importance in VHL disease. Here, we report that a ubiquitin-like molecule called NEDD8 covalently modifies pVHL. A nonneddylateable pVHL mutant, while retaining its ability to ubiquitylate HIF, failed to bind to and promote the assembly of the fibronectin matrix. Expression of the neddylation-defective pVHL in RCC cells, while restoring the regulation of HIF, failed to promote the differentiated morphology in a three-dimensional growth assay and was insufficient to suppress the formation of tumors in SCID mice. These results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and that in the absence of such regulation, an intact HIF pathway is insufficient to prevent VHL-associated tumorigenesis.
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Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1×
“VEC binds and targets specifically prolyl-hydroxylated subunits of hypoxia-inducible factor 1 (HIF-1), HIF-2, and HIF-3 for polyubiquitylation (2, 10 , 12, 19, 20, 22).”
BackgroundSelf-citationOhh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T.-Y., Huang, L. E., Pavletich, N., Chau, V., & Kaelin, W. G. (2000) · Nature Cell Biology · doi:10.1038/35017054 · Cited by 1,577
Self-citationIvan, M., Haberberger, T., Gervasi, D. C., Michelson, K. S., Günzler, V., Kondo, K., Yang, H., Sorokina, I., Conaway, R. C., Conaway, J. W., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192342099 · Cited by 561
Self-citationClifford, S. C. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.10.1029 · Cited by 373
Maynard, M. A., Qi, H., Chung, J., Lee, E. H. L., Kondo, Y., Hara, S., Conaway, R. C., Conaway, J. W., & Ohh, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208681200 · Cited by 283
Self-citation
Cited by
Hypoxia, HIF1 and glucose metabolism in the solid tumour
Denko, N. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2468 · Cited by 1,707
Drug discovery in the ubiquitin–proteasome system
Nalepa, G., Rolfe, M., & Harper, J. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2056 · Cited by 608
Kaelin, W. G. (2007) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.2.010506.092049 · Cited by 336
Self-citationRegulation of Angiogenesis by Hypoxia and Hypoxia‐Inducible Factors
Hickey, M. M., & Simon, M. C. (2006) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(06)76007-0 · Cited by 271
The NEDD8 Conjugation Pathway and Its Relevance in Cancer Biology and Therapy
Soucy, T. A., Dick, L. R., Smith, P. G., Milhollen, M. A., & Brownell, J. E. (2010) · Genes & Cancer · doi:10.1177/1947601910382898 · Cited by 225
Metadata
- Authors
- Stickle, N. H., Chung, J., Klco, J. M., Hill, R. P., Kaelin, W. G., & Ohh, M.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-04-01
- Volume
- 24
- Issue
- 8
- Pages
- 3251-3261
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2170801131
- Cited by
- 185
- References
- 7
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: pVHL Modification by NEDD8 Is Required for Fibronectin Matrix Assembly and Suppression of Tumor Development. https://app.cochat.ai/papers/10.1128/mcb.24.8.3251-3261.2004
- The paper
- Stickle, N. H., Chung, J., Klco, J. M., Hill, R. P., Kaelin, W. G., & Ohh, M. (2004). pVHL Modification by NEDD8 Is Required for Fibronectin Matrix Assembly and Suppression of Tumor Development. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.8.3251-3261.2004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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