Mechanisms of p27^KIP1 inactivation in aggressive B-cell lymphomas.

BCL6 and c-Myc could both contribute to p27^KIP1inactivation through diverse mechanisms, leading to the increased activity of cyclin E–CDK2 complexes. Transcriptional repression ofp27^KIP1, or induction of its proteasomal degradation, causes a decrease in p27^KIP1 levels. Alternatively, in a subset of aggressive lymphomas featuring inactivation of p16^INK4a and/or p21^CIP1, p27^KIP1 is sequestered in an inactive form by cyclin D–CDK4 complexes. K2, CDK2; K4, CDK4; E, cyclin E; D, cyclin D; Ub, ubiquitin.