The role of PACT in mediating gene induction, PKR activation, and apoptosis in response to diverse stimuli.
PACT, the protein activator of the double-stranded (ds)RNA-activated protein kinase (PKR) has been shown to strongly interact with and activate PKR in cultured cells and in vitro. To further analyze the functions of PACT we have recently generated PACT knockout (KO) mice and described several developmental defects that are absent in PKR KO mice. Importantly, PACT has been previously suggested to be involved in different signaling pathways that include endoplasmic reticulum stress, serum deprivation, growth factor withdrawal, viral infection, and cytokine responses. In this study, we have analyzed the contribution of PACT to these pathways using cells derived from wildtype (WT) and PACT KO mice. Notably, we have been unable to detect any significant differences in the responses to stress stimuli comparing WT and PACT KO cells, although we have been able to validate the specific interaction between PACT and PKR. Taken together, our results reinforce the importance of genetic loss of function analysis to infer protein function.
Marques
Joao T
JT
Department of Molecular Genetics, Cleveland Clinic, Cleveland, Ohio 44195, USA.
White
Christine L
CL
Peters
Gregory A
GA
Williams
Bryan R G
BR
Sen
Ganes C
GC
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics; D014709:Vero Cells; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C491290:Rbbp6 protein, mouse; D019892:eIF-2 Kinase