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The von Hippel-Lindau Tumor Suppressor Protein Mediates Ubiquitination of Activated Atypical Protein Kinase C

Open access
Okuda, Heiwa, Saitoh, Kojiro, Hirai, Syu-ichi, Iwai, Kazuhiro, Takaki, Yasuyuki, Baba, Masaya, Minato, Nagahiro, Ohno, Shigeo, Shuin, Taro·2001·Journal of Biological Chemistry

Abstract

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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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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CoChat. (2026). Citation check: The von Hippel-Lindau Tumor Suppressor Protein Mediates Ubiquitination of Activated Atypical Protein Kinase C. https://app.cochat.ai/papers/10.1074/jbc.m107880200
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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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