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Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6
- Source :
- Lissanu Deribe, Y, Wild, P, Chandrashaker, A, Curak, J, Schmidt, M H H, Kalaidzidis, Y, Milutinovic, N, Kratchmarova, I, Buerkle, L, Fetchko, M J, Schmidt, P, Kittanakom, S, Brown, K R, Jurisica, I, Blagoev, B, Zerial, M, Stagljar, I & Dikic, I 2009, ' Regulation of Epidermal Growth Factor Receptor Trafficking by Lysine Deacetylase HDAC6 ', Science Signaling, vol. 2, no. 102, pp. ra84 . https://doi.org/10.1126/scisignal.2000576
- Publication Year :
- 2009
-
Abstract
- Udgivelsesdato: 2009-null 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 two-hybrid system together with bioinformatics to identify 87 candidate proteins interacting with the ligand-unoccupied 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 alpha-tubulin and, subsequently, receptor trafficking along microtubules. A negative feedback loop consisting of EGFR-mediated phosphorylation of HDAC6 Tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-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.
- Subjects :
- Molecular Sequence Data
Endocytosis
Histone Deacetylase 6
Transfection
Biochemistry
Histone Deacetylases
Mass Spectrometry
Cell Line
Epidermal growth factor
Tubulin
Two-Hybrid System Techniques
Humans
Immunoprecipitation
Growth factor receptor inhibitor
Epidermal growth factor receptor
Cloning, Molecular
Receptor
Molecular Biology
biology
Base Sequence
Computational Biology
Acetylation
Cell Biology
HDAC6
Cell biology
ErbB Receptors
Microscopy, Fluorescence
Multiprotein Complexes
biology.protein
RNA
Deacetylase activity
Signal Transduction
Subjects
Details
- ISSN :
- 19379145
- Volume :
- 2
- Issue :
- 102
- Database :
- OpenAIRE
- Journal :
- Science signaling
- Accession number :
- edsair.doi.dedup.....9c57cd63bcb26e37187842cea099af32