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

Keller UB, Old JB, Dorsey FC, Nilsson JA, Nilsson L, MacLean KH, Chung L, Yang C, Spruck C, Boyd K, Reed SI, Cleveland JL
EMBO J. 2007 26 (10): 2562-74

PMID: 17464290 · PMCID: PMC1868903 · DOI:10.1038/sj.emboj.7601691

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.

MeSH Terms (15)

Animals Bone Marrow Cells Burkitt Lymphoma CDC2 Protein Kinase Cell Proliferation Crosses, Genetic Cyclin-Dependent Kinase Inhibitor p27 Humans Lymphoma, B-Cell Mice Mice, Knockout Mice, Transgenic Proto-Oncogene Proteins c-myc Retroviridae Tumor Cells, Cultured

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