Negative regulation of Caenorhabditis elegans epidermal damage responses by death-associated protein kinase.
Wounding of epidermal layers triggers multiple coordinated responses to damage. We show here that the Caenorhabditis elegans ortholog of the tumor suppressor death-associated protein kinase, dapk-1, acts as a previously undescribed negative regulator of barrier repair and innate immune responses to wounding. Loss of DAPK-1 function results in constitutive formation of scar-like structures in the cuticle, and up-regulation of innate immune responses to damage. Overexpression of DAPK-1 represses innate immune responses to needle wounding. Up-regulation of innate immune responses in dapk-1 requires the TIR-1/p38 signal transduction pathway; loss of function in this pathway synergizes with dapk-1 to drastically reduce adult lifespan. Our results reveal a previously undescribed function for the DAPK tumor suppressor family in regulation of epithelial damage responses.
Tong
Amy
A
Department of Molecular, Cell and Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA.
Lynn
Grace
G
Ngo
Vy
V
Wong
Daniel
D
Moseley
Sarah L
SL
Ewbank
Jonathan J
JJ
Goncharov
Alexandr
A
Wu
Yi-Chun
YC
Pujol
Nathalie
N
Chisholm
Andrew D
AD
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D064550:Death-Associated Protein Kinases; D007113:Immunity, Innate; D008854:Microscopy, Electron; D009154:Mutation; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases