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Myc targets Cks1 to provoke the suppression of p27 Kip1 , proliferation and lymphomagenesis
Author(s) -
Keller Ulrich B,
Old Jennifer B,
Dorsey Frank C,
Nilsson Jonas A,
Nilsson Lisa,
MacLean Kirsteen H,
Chung Linda,
Yang Chunying,
Spruck Charles,
Boyd Kelli,
Reed Steven I,
Cleveland John L
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601691
Subject(s) - biology , lymphoma , cancer research , carcinogenesis , skp2 , transgene , kinase , cell growth , cyclin , cell cycle , transcription (linguistics) , cancer , microbiology and biotechnology , gene , ubiquitin ligase , ubiquitin , immunology , genetics , linguistics , philosophy
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 Eμ‐ 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 Eμ‐ Myc B cells, and high levels of Cks1 are also a hallmark of Eμ‐ Myc lymphoma and of human Burkitt lymphoma. Finally, loss of Cks1 in Eμ‐ 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.