title: Apoptosis and cell cycle: distinct checkpoints with overlapping upstream control.
abstract: The question as to whether apoptosis (programmed cell death) is controlled by one or few checkpoints is still unresolved. A growing body of evidence suggests that (one of) the decisive event(s) of cell death consists in the permeabilization of mitochondrial membranes. Indeed, multiple pro-apopotic signal transduction pathways converge on the proteins of the Bcl-2/Bax family which, in concert with the so-called permeability transition pore complex (PTPC), regulate mitochondrial membrane barrier function. Mitochondrial permeabilization causes the release of soluble intermembrane proteins, some of which are involved in the activation of apoptotic proteases and nucleases. Thus, the putative checkpoint determining the death/life decision is clearly different from the known checkpoints of cell cycle progression. Prominent oncogenes (e.g., c-Myc, Ras, Raf, Bcl-2) and tumor suppressor genes (e.g., p53, Bax) have been shown to modulate apoptosis via a direct or indirect effect on mitochondrial membranes. All these oncoproteins and tumor suppressor proteins may simultaneously influence the cell cycle and the propensity to undergo apoptosis. Several cell cycle regulatory proteins (e.g., cyclins, cdk, etc.) can induce or inhibit apoptosis via yet unknown pathways.
authors.affiliation: Centre national de la recherche scientifique, ERS 1984, Villejuif, France.
authors.forename: E
authors.initials: E
authors.lastname: Jacotot
authors.forename: K F
authors.initials: KF
authors.lastname: Ferri
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D009857:Oncogenes
chemical_list: D018797:Cell Cycle Proteins