Journal Article

Signaling through cyclin D-dependent kinases

Anders, L, Choi, Y J

2014

Overview

Research over the past quarter century has identified cyclin D-dependent kinases, CDK4 and CDK6, as the major oncogenic drivers among members of the CDK superfamily. CDK4/6 are rendered hyperactive in the majority of human cancers through a multitude of genomic alterations. Sustained activation of these protein kinases provides cancer cells with the power to enter the cell cycle continuously by triggering G1-S-phase transitions and dramatically shortening the duration of the G1 phase. It has also become clear, however, that CDK4/6 effectively counter cancer cell-intrinsic tumor suppression mechanisms, senescence and apoptosis, which must be overcome during cell transformation and kept at bay throughout all stages of tumorigenesis. As a central ‘node’ in cellular signaling networks, cyclin D-dependent kinases sense a plethora of mitogenic signals to orchestrate specific transcriptional programs. As the complexity of the cellular signaling network regulated by these oncogenic kinases unfolds, much remains to be learned about its architecture, its dynamics and the consequences of its perturbation.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/45/275 / 631/80/509 / 631/80/82/23 / 631/80/86 / Animals / Apoptosis / Carcinogenesis / Cell Biology / Cell cycle / Cell Cycle - physiology / Cell Transformation, Neoplastic - metabolism / Cyclin D / Cyclin D - metabolism / Cyclin-dependent kinase 4 / Cyclin-Dependent Kinases - metabolism / Cyclins / G1 phase / Gene expression / Human Genetics / Humans / Internal Medicine / Kinases / Medicine / Medicine & Public Health / Oncology / Phase transitions / Phosphotransferases / Physiological aspects / Protein kinase / Protein Unfolding / review / Senescence / Signal transduction / Signal Transduction - physiology / Transcription / Tumor suppression / Tumorigenesis