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Is cell cycle arrest needed for apoptosis to occur? I note that some of the factors that mediate cell cycle arrest induction (e.g. DNA damage) happen to be responsible for initiating apoptosis as well. However can apoptosis occur without first arresting the cell cycle?

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  • $\begingroup$ As I remember, apoptosis is generally triggered by mitochondrial membrane being destroyed. I don't think cell cycle arrest is necessary to trigger this process. $\endgroup$ – Roni Saiba Mar 4 '18 at 17:34
  • $\begingroup$ @RoniSaiba not necessarily... that would generally be the pathway for the intrinsic pathway of apoptosis (release of cytochrome C from mitochondrial IM space), but it doesn't necessarily apply for the extrinsic pathway. $\endgroup$ – anonymous2 Jan 21 at 22:02
  • $\begingroup$ For context, realize that a large proportion of cells in complex multicellular organisms (for which apoptosis is relevant) are in G0 for most of their life. Cell cycle arrest is the norm. $\endgroup$ – De Novo Jan 21 at 22:42
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Apoptosis can occur without cell cycle already being arrested. For instance, in the case of extrinsic apoptosis, which could be induced by T lymphocytes, for example, a trimeric receptor such as TNF-R or TRAIL-R's containing a DD can be bound at any time by the death ligand secreted by (TNF, TRAIL) or bound to the immune cell membrane (FasL, TRAIL).

The DD (death domain), independent of where cell cycle is, recruits adaptor proteins with DED domains (ie., FADD), which in turn recruit procaspase 8. Procaspase 8 is cross-activated (becoming caspase 8) when two of them are recruited, then released. It then begins activating procaspases 3, which begins the actual work of killing the cell (cutting cytoskeleton => blebbing, etc.), activating CAD.

It bears mentioning, however, that once it's kicked in, cell cycle will inevitably stop, since CAD will start fragmenting the DNA... It also bears mentioning that caspase 8 also activates the intrinsic pathway via Bid => tBid => Bax => Bak => mitochondrial leakage, cytochrome C activating caspase 9...


Sources:

  • Sayers, Thomas J. 2011. Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunology, Immunotherapy 60 (8): 1173-80.

  • Eimon, P. M., E. Kratz, E. Varfolomeev, S. G. Hymowitz, H. Stern, J. Zha, and A. Ashkenazi. 2006. Delineation of the cell-extrinsic apoptosis pathway in the zebrafish. Cell Death and Differentiation 13 (10): 1619-30.

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