Loss of CBP causes T cell lymphomagenesis in synergy with p27 Kip1 insufficiency

Ningling Kang-Decker, Caili Tong, Fayçal Boussouar, Darren J. Baker, Wu Xu, Alexey A. Leontovich, William R. Taylor, Paul K. Brindle, Jan M.A. Van Deursen

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

CBP can function as a tumor suppressor, but the mechanisms that govern oncogenesis in its absence are unknown. Here we show that CBP inactivation in mouse thymocytes leads to lymphoma. Although CBP has been implicated in the transactivation functions of p53, development of these tumors does not seem to involve loss of p53 activity. CBP-null tumors show reduced levels of p27 Kip1 and increased levels of cyclin E and Skp2, two oncoproteins that can promote p27Kip1 proteolysis. Reduction of p27 Kip1 by introduction of a p27Kip1-null allele into CBP knockout mice accelerates lymphomagenesis and seems to obviate the requirement for Skp2 and cyclin E upregulation. These data suggest that CBP loss mediates lymphomagenesis in cooperation with a mechanism that reduces p27Kip1 abundance.

Original languageEnglish (US)
Pages (from-to)177-189
Number of pages13
JournalCancer cell
Volume5
Issue number2
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Kang-Decker, N., Tong, C., Boussouar, F., Baker, D. J., Xu, W., Leontovich, A. A., Taylor, W. R., Brindle, P. K., & Van Deursen, J. M. A. (2004). Loss of CBP causes T cell lymphomagenesis in synergy with p27 Kip1 insufficiency. Cancer cell, 5(2), 177-189. https://doi.org/10.1016/S1535-6108(04)00022-4