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Cited by 334

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

Activation of Protein Kinase C Triggers Its Ubiquitination and Degradation

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Lu, Zhimin, Liu, David, Hornia, Armand, Devonish, Wayne, Pagano, Michele, Foster, David A.·1998·Molecular and Cellular Biology

Abstract

Treatment of cells with tumor-promoting phorbol esters results in the activation but then depletion of phorbol ester-responsive protein kinase C (PKC) isoforms. The ubiquitin-proteasome pathway has been implicated in regulating the levels of many cellular proteins, including those involved in cell cycle control. We report here that in 3Y1 rat fibroblasts, proteasome inhibitors prevent the depletion of PKC isoforms alpha, delta, and epsilon in response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Proteasome inhibitors also blocked the tumor-promoting effects of TPA on 3Y1 cells overexpressing c-Src, which results from the depletion of PKC delta. Consistent with the involvement of the ubiquitin-proteasome pathway in the degradation of PKC isoforms, ubiquitinated PKC alpha, delta, and epsilon were detected within 30 min of TPA treatment. Diacylglycerol, the physiological activator of PKC, also stimulated ubiquitination and degradation of PKC, suggesting that ubiquitination is a physiological response to PKC activation. Compounds that inhibit activation of PKC prevented both TPA- and diacylglycerol-induced PKC depletion and ubiquitination. Moreover, a kinase-dead ATP-binding mutant of PKC alpha could not be depleted by TPA treatment. These data are consistent with a suicide model whereby activation of PKC triggers its own degradation via the ubiquitin-proteasome pathway.

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Metadata

Authors
Lu, Z., Liu, D., Hornia, A., Devonish, W., Pagano, M., & Foster, D. A.
Venue
Molecular and Cellular Biology
Published
1998-02-01
Volume
18
Issue
2
Pages
839-845
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2155603822
Cited by
334
References
19
FWCI
4.61
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Activation of Protein Kinase C Triggers Its Ubiquitination and Degradation. https://app.cochat.ai/papers/10.1128/mcb.18.2.839
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Lu, Z., Liu, D., Hornia, A., Devonish, W., Pagano, M., & Foster, D. A. (1998). Activation of Protein Kinase C Triggers Its Ubiquitination and Degradation. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.18.2.839

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