Presenilin 1 independently regulates beta-catenin stability and transcriptional activity

The Journal of Biological Chemistry
R KillickB H Anderton

Abstract

Presenilin 1 (PS1) regulates beta-catenin stability; however, published data regarding the direction of the effect are contradictory. We examined the effects of wild-type and mutant forms of PS1 on the membrane, cytoplasmic, nuclear, and signaling pools of endogenous and exogenous beta-catenin by immunofluorescence microscopy, subcellular fractionation, and in a transcription assay. We found that PS1 destabilizes the cytoplasmic and nuclear pools of beta-catenin when stabilized by Wnt or Dvl but not when stabilized at lower levels of the Wnt pathway. The PS1 mutants examined were less able to reduce the stability of beta-catenin. PS1 also inhibited the transcriptional activity of endogenous beta-catenin, and the PS1 mutants were again less inhibitory at the level of Dvl but showed a different pattern of inhibition toward transcription below Dvl. The transcriptional activity of exogenously expressed wild-type beta-catenin and two mutants, DeltaN89beta-catenin and DeltaSTbeta-catenin, were also inhibited by wild-type and mutant PS1. We conclude that PS1 negatively regulates the stability and transcriptional activity of beta-catenin at different levels in the Wnt pathway, that the effect on transcriptional activity appears to be i...Continue Reading

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Citations

Aug 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jia-Ling TeoMichael Kahn
Jan 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jie Shen, Raymond J Kelleher
Aug 30, 2005·The Journal of Biological Chemistry·Geo SerbanNikolaos K Robakis
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Apr 19, 2003·Acta Oto-laryngologica·Ruediger ThalmannIsolde Thalmann
Jun 9, 2021·Neural Regeneration Research·Mercedes A Hernandez-SapiensAlejandro A Canales-Aguirre
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Dec 17, 2008·Seminars in Cell & Developmental Biology·Matthew R HassGuojun Zhao

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