A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis
Year: 2013
Type: article
Abstract: In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a.
Source: Cancer Cell
Authors: Karoline Kollmann, Gerwin Heller, Christine Schneckenleithner, Wolfgang Warsch, Ruth Scheicher, Rene G. Ott, Markus Schäfer, Sabine Fajmann, Michaela Schlederer, Ana-Iris Schiefer, Ursula Reichart, Matthias Mayerhofer, Christoph Hoeller, Sabine Zöchbauer-Müller, Dontscho Kerjaschki, Christoph Bock, Lukas Kenner, Gerald Hoefler, Michael Freissmuth, Anthony R. Green, Richard Moriggl, Meinrad Busslinger, Marcos Malumbres, Veronika Sexl
Institutions: University of Veterinary Medicine Vienna, Comprehensive Cancer Center Vienna, Medical University of Vienna, Research Institute of Molecular Pathology, Vienna Biocenter, Austrian Academy of Sciences, CeMM Research Center for Molecular Medicine, Ludwig Boltzmann Institute for Cancer Research, Medical University of Graz, Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Addenbrooke's Hospital, Wellcome Trust, Spanish National Cancer Research Centre
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,810
OpenAlex ID: W2152600133