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Seminar (1 Sept 2009)

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Seminar

Driving Biological Discoveries Using the

Membrane Yeast Two-Hybrid (MYTH) Technology:

lessons from the human Epidermal Growth Factor Receptor (EGFR)


By

Dr. Igor Stagljar

Associate Professor

Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR)

Department of Biochemistry & Department of Molecular Genetics

University of Toronto, Canada



1 September 2009 (Tue)

3:00 - 4:00 pm




Room L6-32, 6/F, Laboratory Block

Li Ka Shing Faculty of Medicine Building

21 Sassoon Road, Pokfulam, Hong Kong

 
 

Abstract:

Binding of epidermal growth factor (EGF) to its receptor (EGFR) leads to receptor dimerization, assembly of protein complexes and activation of signalling networks that control key physiological cell responses. Despite their fundamental role in cell biology, little is known about protein complexes associated with the EGFR prior to growth factor stimulation. We utilized modified membrane yeast two-hybrid system to identify 87 candidate proteins interacting with the ligand-unoccupied EGFR. Among them is HDAC6, a cytoplasmic histone deacetylase, which negatively regulates EGFR endocytosis and degradation by controlling the acetylation status of alpha-tubulin and subsequently receptor trafficking along microtubules. A negative feedback loop imposed by phosphorylation of HDAC6 Tyr570 by EGFR activation resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin. This study demonstrates the power and sensitivity of MYTH coupled with bioinformatics that led to the identification of HDAC6 as a novel binding partner of EGFR, a well characterized oncogenic driver. It also illustrates an unprecedented complexity of the EGFR associated interactome and identifies protein acetylation as a novel regulatory mechanism for receptor endocytosis and degradation.

 


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