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- Title
Regulation of Epidermal Growth Factor Receptor Trafficking by Lysine Deacetylase HDAC6.
- Authors
Deribe, Yonathan Lissanu; Wild, Philipp; Chandrashaker, Akhila; Curak, Jasna; Schmidt, Mirko H. H.; Kalaidzidis, Yannis; Milutinovic, Natasa; Kratchmarova, Irina; Buerkle, Lukas; Fetchko, Michael J.; Schmidt, Philipp; Kittanakom, Saranya; Brown, Kevin R.; Jurisica, Igor; Blagoev, Blagoy; Zeria, Marino; Stagljar, Igor; Dikic, Ivan
- Abstract
Binding of epidermal growth factor (EGF) to its receptor leads to receptor dimerization, assembly of protein complexes, and activation of signaling networks that control key cellular responses. Despite their fundamental role in cell biology, little is known about protein complexes associated with the EGF receptor (EGFR) before growth factor stimulation. We used a modified membrane yeast twohybrid system together with bioinformatics to identify 87 candidate proteins interacting with the ligandunoccupied EGFR. Among them was histone deacetylase 6 (HDAC6), a cytoplasmic lysine deacetylase, which we found negatively regulated EGFR endocytosis and degradation by controlling the acetylation status of α-tubulin and, subsequently, receptor trafficking along microtubules. A negative feedback loop consisting of EGFR-mediated phosphorylation of HDAC6 Tyr570 resulted in reduced deacetylase activity and increased acetylation of α-tubulin. This study illustrates the complexity of the EGFR-associated interactome and identifies protein acetylation as a previously unknown regulator of receptor endocytosis and degradation.
- Publication
Science Signaling, 2009, Vol 2, Issue 102, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.2000576