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Three papers published concurrently in the October issue of Nature Medicine have demonstrated new links between mitogenic cytokine signalling and the cell cycle inhibitor p27KIP1, and have elucidated how this link may contribute to breast cancer patient prognosis [1-3].  Cell cycle control occurs through cyclin binding to the cyclin-dependent kinases (CDKs) that stimulate G1 progression [4]. p27KIP1 is a member of the kinase inhibitor protein (KIP) family that inhibit cell cycle progression by binding to cyclin-CDK complexes [5]. In cancers where protein kinase B (PKB)/Akt is constitutively activated by upstream oncogenes, Akt decreases p27KIP1 by increasing proteolysis and reducing transcription [6].  These three articles describe a third way in which Akt resists G1 arrest, namely by a p27KIP1 phosphorylation that impairs nuclear import and prevents its inhibition of cyclin-CDK complexes. The authors of these studies conclude that exclusion of p27KIP1 from the nucleus leads to a poor patient outcome in breast cancer [1-3].

p27KIP1phosphorylation by PKB/Akt leads to poor breast cancer prognosis