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  Protein Phosphatase 2A and Rapamycin regulate the nuclear localization and activity of the transcription factor GLI3

Krauß, S., Foerster, J., Schneider, R., & Schweiger, S. (2008). Protein Phosphatase 2A and Rapamycin regulate the nuclear localization and activity of the transcription factor GLI3. Cancer Research, 68(12), 4658-4665. Retrieved from http://cancerres.aacrjournals.org/cgi/reprint/68/12/4658.

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Genre: Journal Article
Alternative Title : Cancer Res

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4658.pdf (Any fulltext), 439KB
 
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 Creators:
Krauß, Sybille1, Author
Foerster, John, Author
Schneider, Rainer2, Author           
Schweiger, Susann2, Author           
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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 Abstract: Gain-of-function alterations to the sonic hedgehog (SHH) signaling cascade have been found in a wide range of tumors. Three SHH effectors, GLI1, GLI2, and GLI3, regulate transcription of diverse genes involved in cell growth and cell proliferation. Here, we show that protein phosphatase 2A (PP2A), its regulatory subunit, alpha4, and rapamycin, an inhibitor of the mammalian target of rapamycin kinase complex 1 (mTORC1), regulate the nuclear localization and transcriptional activity of GLI3. An increase in PP2A activity or treatment with rapamycin leads to cytosolic retention of GLI3 and, consequently, reduced transcription of the GLI3 target gene and cell cycle regulator, cyclin D1. Conversely, inhibition of PP2A results in increased expression of cyclin D1. In summary, our findings reveal the existence of a hitherto unrecognized molecular cross-talk between the oncogenic SHH pathway and the tumor suppressor PP2A and suggest a novel mechanism underlying the anticancerogenic effects of rapamycin.

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Language(s): eng - English
 Dates: 2008-06-15
 Publication Status: Issued
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Title: Cancer Research
  Alternative Title : Cancer Res
Source Genre: Journal
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Pages: - Volume / Issue: 68 (12) Sequence Number: - Start / End Page: 4658 - 4665 Identifier: -