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Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation

Haglund, Kaisa, Sigismund, Sara, Polo, Simona, Szymkiewicz, Iwona, Di Fiore, Pier Paolo, Dikic, Ivan·2003·Nature Cell Biology
DOI 10.1038/ncb983
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Abstract

Many cellular proteins are post-translationally modified by the addition of a single ubiquitin or a polyubiquitin chain. Among these are receptor tyrosine kinases (RTKs), which undergo ligand-dependent ubiquitination. The ubiquitination of RTKs has become recognized as an important signal for their endocytosis and degradation in the lysosome; however, it is not clear whether ubiquitination itself is sufficient for this process or simply participates in its regulation. The issue is further complicated by the fact that RTKs are thought to be polyubiquitinated - a modification that is linked to protein degradation by the proteasome. By contrast, monoubiquitination has been associated with diverse proteasome-independent cellular functions including intracellular protein movement. Here we show that the epidermal growth factor and platelet-derived growth factor receptors are not polyubiquitinated but rather are monoubiquitinated at multiple sites after their ligand-induced activation. By using different biochemical and molecular genetics approaches, we show that a single ubiquitin is sufficient for both receptor internalization and degradation. Thus, monoubiquitination is the principal signal responsible for the movement of RTKs from the plasma membrane to the lysosome.

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Research works printed but not linked: 30

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Metadata

Authors
Haglund, K., Sigismund, S., Polo, S., Szymkiewicz, I., Di Fiore, P. P., & Dikic, I.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2003-04-28
Volume
5
Issue
5
Pages
461-466
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb983
Cited by
715
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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