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Type of publication: Journal Article
Type of document: Full Paper

Year: 2013

Authors: Kollmann, K; Heller, G; Schneckenleithner, C; Warsch, W; Scheicher, R; Ott, RG; Schäfer, M; Fajmann, S; Schlederer, M; Schiefer, AI; Reichart, U; Mayerhofer, M; Hoeller, C; Zöchbauer-Müller, S; Kerjaschki, D; Bock, C; Kenner, L; Hoefler, G; Freissmuth, M; Green, AR; Moriggl, R; Busslinger, M; Malumbres, M; Sexl, V

Title: A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis.

Source: Cancer Cell. 2013; 24(2):167-181



Authors Vetmeduni Vienna:

Kenner Lukas
Kollmann Karoline
Moriggl Richard
Reichart Ursula
Scheicher Ruth
Schneckenleithner Christine
Sexl Veronika
Warsch Wolfgang

Vetmed Research Units
Institute of Animal Breeding and Genetics
Institute of Pharmacology and Toxicology


Project(s): Flow cytometric signal typing for therapy response

Uncoupling CDK6 from p16INK4A- effects for hematopoiesis and lymphomagenesis


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.

Keywords Pubmed: Animals
Cell Cycle/physiology
Cyclin-Dependent Kinase 6/genetics
Cyclin-Dependent Kinase 6/metabolism*
Humans
Leukemia, B-Cell/enzymology
Leukemia, B-Cell/pathology
Lymphoma, B-Cell/enzymology
Lymphoma, B-Cell/pathology
Mice
Mice, Inbred C57BL
Mice, Nude
Mice, Transgenic
Neoplasms/blood supply*
Neoplasms/enzymology*
Neoplasms/genetics
Neovascularization, Pathologic/enzymology
Neovascularization, Pathologic/pathology


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