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Publication : Myc targets Cks1 to provoke the suppression of p27Kip1, proliferation and lymphomagenesis.

First Author  Keller UB Year  2007
Journal  EMBO J Volume  26
Issue  10 Pages  2562-74
PubMed ID  17464290 Mgi Jnum  J:121564
Mgi Id  MGI:3710462 Doi  10.1038/sj.emboj.7601691
Citation  Keller UB, et al. (2007) Myc targets Cks1 to provoke the suppression of p27(Kip1), proliferation and lymphomagenesis. EMBO J 26(10):2562-74
abstractText  Reduced levels of the cyclin-dependent kinase inhibitor p27(Kip1) connote poor prognosis in cancer. In human Burkitt lymphoma and in precancerous B cells and lymphomas arising in Emu-Myc transgenic mice, p27(Kip1) expression is markedly reduced. We show that the transcription of the Cks1 component of the SCF(Skp2) complex that is necessary for p27(Kip1) ubiquitylation and degradation is induced by Myc. Further, Cks1 expression is elevated in precancerous Emu-Myc B cells, and high levels of Cks1 are also a hallmark of Emu-Myc lymphoma and of human Burkitt lymphoma. Finally, loss of Cks1 in Emu-Myc B cells elevates p27(Kip1) levels, reduces proliferation and markedly delays lymphoma development and dissemination of disease. Therefore, Myc suppresses p27(Kip1) expression, accelerates cell proliferation and promotes tumorigenesis at least in part through its ability to selectively induce Cks1.
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