From sentencing to execution--the processes of apoptosis.
OBJECTIVE
Cell proliferation and apoptosis play a major role in maintaining homeostasis and as such any disruption within these processes can lead to disease states. Apoptosis occurs in three non-distinct phases--induction, effector and degradation--and can be executed through both the extrinsic and intrinsic pathways in addition to recognised sub-pathways such as the p53 and lysosomal pathways. This review article highlights these pathways, incorporating an overview of the molecular regulators of apoptosis.


RESULTS
These regulators include the prominent apoptotic players 'the caspases' in addition to the main regulators of the Bcl-2 family. Increased understanding of the physiological processes of apoptosis at the molecular level not only offers an insight in disease pathogenesis but, in addition, allows for the development of diagnostic, prognostic and therapeutic tools.


CONCLUSIONS
While apoptosis remains the key player in cellular death, other processes cannot be dismissed. Many other proteins, in addition to caspases, within apoptotic pathways have been identified. Research continues into establishing the precise aspects of their molecular mechanisms of action and inter-relationships. Inappropriate apoptosis due to dysregulation of cell death pathways provides a plethora of molecular checkpoints that can be targeted and modulated as part of therapeutic intervention. Increased research into these areas will prove useful for the design of novel chemotherapeutic drugs, an area that is particularly important due to increased risk of chemoresistance.
Moffitt
Kelly L
KL
Biomolecular Sciences Group, School of Pharmacy, Queen's University of Belfast, Belfast, Northern Ireland, UK. k.moffitt@qub.ac.uk
Martin
S Lorraine
SL
Walker
Brian
B
D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases