Suppression of nuclear Wnt signaling leads to stabilization of Rac1 isoforms |
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Authors: | Esufali Susmita Charames George S Bapat Bharati |
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Institution: | Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Room L6-304-4, Toronto, Canada. |
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Abstract: | 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. |
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Keywords: | D-box destruction box DNTCF4 dominant-negative TCF4 NLS nuclear localization signal PBR polybasic region |
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