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  • The EMBO Journal (2007) 26, 2562 - 2574
  • doi:10.1038/sj.emboj.7601691

Published online: 26 April 2007

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

Ulrich B Keller1,5, Jennifer B Old1,a, Frank C Dorsey1,2, Jonas A Nilsson1,b, Lisa Nilsson1,b, Kirsteen H MacLean1, Linda Chung1, Chunying Yang1, Charles Spruck3, Kelli Boyd4, Steven I Reed3 and John L Cleveland1,2

  1. Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN, USA
  2. Department of Cancer Biology, The Scripps Research Institute-Florida, Jupiter, FL, USA
  3. Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA
  4. Animal Resource Center, St Jude Children's Research Hospital, Memphis, TN, USA
  5. III Medical Department, Technical University Munich, Munich, Germany

Correspondence to:

John L Cleveland, Department of Cancer Biology, The Scripps Research Institute-Florida, 5353 Parkside Drive, Jupiter, FL 33458, USA. Tel.: +1 561 799 8795; Fax: +1 561 799 8957; E-mail: jcleve@scripps.edu

aPresent address: Independent Forensics Research and Development Scientists, 4600 West Roosevelt Road, Hillside, IL 60162, USA

bPresent address: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden

Received 6 September 2006; Accepted 28 March 2007

Reduced levels of the cyclin-dependent kinase inhibitor p27Kip1 connote poor prognosis in cancer. In human Burkitt lymphoma and in precancerous B cells and lymphomas arising in Emu-Myc transgenic mice, p27Kip1 expression is markedly reduced. We show that the transcription of the Cks1 component of the SCFSkp2 complex that is necessary for p27Kip1 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 p27Kip1 levels, reduces proliferation and markedly delays lymphoma development and dissemination of disease. Therefore, Myc suppresses p27Kip1 expression, accelerates cell proliferation and promotes tumorigenesis at least in part through its ability to selectively induce Cks1.

  • Keywords:

    • Cks1,
    • lymphomagenesis,
    • Myc,
    • p27Kip1,
    • proliferation