Activation of p53 by Dishevelled independent of Wnt or planar polarity pathways.
Dishevelled is a key component of the Wnt signaling and planar polarity pathways. We discovered that in selective cell types, it potently activates the transcriptional activity of the tumor suppressor p53. This action, however, is not dependent on the downstream of either the Wnt or the planar polarity pathways. Dishevelled signals to the first 50 amino acids of p53, which is the transactivation domain. The level of phosphorylation on several serine residues within that region of p53 increases in response to disheveled activation, partially contributing to p53 activation. The MAP kinase pathway and E1B55k may also be involved in this dishevelled-p53 connection. Our data provide evidence that there is a novel signaling pathway from Dishevelled to p53.
Ding
Vivianne W
VW
UCSF Comprehensive Cancer Center, Cancer Research Institute, 2340 Sutter Street, San Francisco, CA 94115, USA.
Lin
Li-Ping
LP
Chiang
Andrew L
AL
McCormick
Frank
F
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017501:Adenovirus E1B Proteins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D000072261:Dishevelled Proteins; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D017501:Adenovirus E1B Proteins; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases