Novel insights into DAPK autophagic signalling using peptide aptamer combinatorial protein-interaction screens

Stevens, Craig; Hupp, Ted R.

Abstract

DAPK represents a relatively unique enzyme in the protein kinase superfamily whose major biological functions are linked to both autophagy and signal-mediated apoptosis. However, genetic studies have not yet uncovered how DAPK integrates into the core autophagy-related (Atg) machinery since DAPK is not present in a genetically tractable eukaryotic cell such as yeast. Furthermore, there have been no definitive DAPK binding proteins identified in metazoan systems that play a direct role in cooperating with DAPK in autophagy. We have utilized a growing concept in systems biology that invokes linear peptide-motifs as a fundamental mechanism driving protein-protein interactions and as a key switch underlying the dynamics of a signal transduction pathway. By using peptide combinatorial libraries as an assay that reflects the diversity of the linear peptide motif repertoire in the mammalian proteome, we identified microtubule-associated protein 1B (MAP1B) as a novel DAPK interacting protein that stimulates DAPK-dependent membrane blebbing and autophagy.MAP1B has previously been shown to form a functional interaction with the autophagosomal protein Atg8 (LC3). Together these studies define a genetic interaction between DAPK-MAP1B in the regulation of autophagy that may have particular relevance to cellular signalling pathways that regulate cell survival or cell death under distinct environmental stresses.

Citation

Stevens, C. & Hupp, T. R. (2008). Novel insights into DAPK autophagic signalling using peptide aptamer combinatorial protein-interaction screens. Autophagy. 4. (4). 531-533. doi:10.4161/auto.5940. ISSN 1554-8627.

• Journal Article Type: Article
• Online Publication Date: Apr 4, 2008
• Publication Date: May 16, 2008
• Deposit Date: Aug 5, 2016
• Journal: Autophagy
• Print ISSN: 1554-8627
• Electronic ISSN: 1554-8635
• Publisher: Taylor & Francis
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 4
• Pages: 531-533
• DOI: https://doi.org/10.4161/auto.5940
• Keywords: Cell Biology; Molecular Biology
• Public URL: http://researchrepository.napier.ac.uk/Output/328390
• Additional Information: Addendum to: Harrison B, Kraus M, Burch L, Stevens C, Craig A, Gordon-Weeks P, Hupp T. DAPK-1 binding to a linear interaction motif in MAP1B stimulates autophagy and membrane blebbing. J Biol Chem 2008; In press.