The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
The von Hippel-Lindau Tumor Suppressor Protein Mediates Ubiquitination of Activated Atypical Protein Kinase C
Open accessAbstract
The von Hippel-Lindau tumor-suppressor protein (pVHL) forms a protein complex (VCB-Cul2) with elongin C, elongin B, Cul-2, and Rbx1, which functions as a ubiquitin-protein ligase (E3). The alpha-subunits of the hypoxia-inducible factors have been identified as targets for the VCB-Cul2 ubiquitin ligase. However, a variety of cellular defects caused by the depletion of pVHL cannot be explained solely by the ubiquitin-mediated degradation of hypoxia-inducible factor-alpha. We show here that a member of the atypical protein kinase C (PKC) group, PKClambda, is ubiquitinated by the pVHL-containing E3 enzyme. An active PKClambda mutant is ubiquitinated more extensively than wild-type PKClambda in HEK293 cells, and the ubiquitination is further enhanced by the overexpression of pVHL. The activation of wild-type PKClambda by serum stimulation of cells enhances the ubiquitination of the protein, supporting the notion that active PKClambda is preferentially ubiquitinated by VCB-Cul2 ubiquitin ligase. Furthermore, we show that PKClambda can be ubiquitinated in vitro in a cell-free ubiquitination assay using purified recombinant components including VCB-Cul2. Given the known function of aPKC in the regulation of cell polarity and cell growth, PKClambda may be a target of pVHL in its function as a tumor suppressor.
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
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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
Protein kinase C and lipid signaling for sustained cellular responses
Nishizuka, Y. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.7.7737456 · Cited by 2,499
Ohh, 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
The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42
Joberty, G., Petersen, C., Gao, L., & Macara, I. G. (2000) · Nature Cell Biology · doi:10.1038/35019573 · Cited by 928
A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity
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Cited by
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865
Derailed endocytosis: an emerging feature of cancer
Mosesson, Y., Mills, G. B., & Yarden, Y. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2521 · Cited by 718
Lee, S., Nakamura, E., Yang, H., Wei, W., Linggi, M. S., Sajan, M. P., Farese, R. V., Freeman, R. S., Carter, B. D., Kaelin, W. G., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.015 · Cited by 527
Elvidge, G. P., Glenny, L., Appelhoff, R. J., Ratcliffe, P. J., Ragoussis, J., & Gleadle, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511408200 · Cited by 464
Cell polarity in development and cancer
Wodarz, A., & Näthke, I. (2007) · Nature Cell Biology · doi:10.1038/ncb433 · Cited by 395
Metadata
- Authors
- Okuda, H., Saitoh, K., Hirai, S.-I., Iwai, K., Takaki, Y., Baba, M., Minato, N., Ohno, S., & Shuin, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 276
- Issue
- 47
- Pages
- 43611-43617
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1970078605
- Cited by
- 176
- References
- 8
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Okuda, H., Saitoh, K., Hirai, S.-I., Iwai, K., Takaki, Y., Baba, M., Minato, N., Ohno, S., & Shuin, T. (2001). The von Hippel-Lindau Tumor Suppressor Protein Mediates Ubiquitination of Activated Atypical Protein Kinase C. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m107880200
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