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

Craig Stevens, Ted R Hupp

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)531-3
Number of pages3
JournalAutophagy
Volume4
Issue number4
Publication statusPublished - May 2008

Keywords

  • Amino Acid Motifs
  • Animals
  • Apoptosis Regulatory Proteins
  • Aptamers, Peptide
  • Autophagy
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Death-Associated Protein Kinases
  • Microtubule-Associated Proteins
  • Neurons
  • Protein Binding
  • Protein Interaction Mapping
  • Signal Transduction

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