Suppression of nuclear Wnt signaling leads to stabilization of Rac1 isoforms.
The Rac1 GTPase contains a functional nuclear localization signal (NLS) and destruction box sequence in the C-terminal polybasic region. It has been postulated that these two regulatory sequences may function together, enabling Rac1 to participate in nuclear signaling pathways that ultimately target it for degradation. We have previously shown that the NLS activity of Rac1 and the Rac1b splice variant is essential for Wnt pathway activation. In the present study, we demonstrate that suppression of nuclear Wnt signaling leads to stabilization of Rac1 protein. In addition, we show that Rac1b may be under proteasomal regulation. We propose that Rac1 and Rac1b levels are regulated by being targeted for degradation through a negative feedback loop initiated by Wnt signaling.
Esufali
Susmita
S
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Room L6-304-4, Toronto, Canada.
Charames
George S
GS
Bapat
Bharati
B
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D061988:Proteasome Inhibitors; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D061988:Proteasome Inhibitors; D020033:Protein Isoforms; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins; D020830:rac1 GTP-Binding Protein