The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9.
The planar cell polarity (PCP) pathway, a beta-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks beta-catenin-dependent and promotes beta-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.
Haribaskar
Ramachandran
R
Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, Freiburg, Germany.
Pütz
Michael
M
Schupp
Birte
B
Skouloudaki
Kassiani
K
Bietenbeck
Andreas
A
Walz
Gerd
G
Schäfer
Tobias
T
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D016764:Cell Polarity / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000378:metabolism
C464902:ANKRD6 protein, human; C464903:Ankrd6 protein, mouse; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C489901:MLLT3 protein, human; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D051153:Wnt Proteins; D048670:MAP Kinase Kinase 4