Cell senescence and hypermitogenic arrest.
A diverse range of conditions, from mitogenic stimuli to cytotoxic stress, can induce cell senescence. Here, I propose that simultaneous stimulation of mitogen-activated pathways and downstream inhibition of cyclin-dependent kinases leads, ultimately, to cell senescence. This model distinguishes between two types of growth arrest: first, exit to G0 phase, which is caused by the withdrawal of mitogens and can lead to apoptosis; and second, hypermitogenic arrest, which is stimulated by mitogens and can lead to senescence. The concept of hypermitogenic arrest defines cell senescence as a functionally active, stable and conditionally reversible state.
Blagosklonny
Mikhail V
MV
Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA. m_blagosklonny@nymc.edu
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D008938:Mitosis; D015398:Signal Transduction / Q000502:physiology
D018844:Cyclin-Dependent Kinases