title: Post-translational regulation of the cellular levels of DAPK.
abstract: Death associated protein kinase (DAPK) is a large, multi-domain ser/thr kinase whose activities converge upon multiple signaling pathways that regulate autophagy, caspase-dependent cell death, cell adhesion and migration. The cellular levels of DAPK are post-translationally regulated by the combined activities of two degradation systems, including the ubiquitin proteasome and an extra-lysosomal proteolysis pathway. At least three distinct E3 ubiquitin ligases target DAPK, including mindbomb1, the chaperone dependent ligase, CHIP (carboxy terminus of Hsp70-interacting protein) and a cullin RING ligase complex, KLHL20-Cul3-RBX1. In addition, it appears that the cellular levels of DAPK are also regulated by an extra-lysosomal protease, cathepsin B. While protein quality control and recycling clearly benefit cells by removal of misfolded or toxic proteins and recycling of their components, the finding that multiple surveillance systems target DAPK suggests that these protein degradation systems also act to fine tune DAPK expression levels in response to specific signaling pathways.
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA, pgallag@iupui.edu.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Gallagher
authors.forename: Emily K
authors.initials: EK
authors.lastname: Blue
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D064550:Death-Associated Protein Kinases; D002401:Cathepsin B; D046988:Proteasome Endopeptidase Complex