gocentral
commented
16 years ago Logged In: YES user_id=865072 Originator: NO
Peter,
I have argued for a long time about the need for a review and reorganization of GO apoptosis terms and made the suggestion that an actual GO Content meeting involving domain experts might be the appropriate approach to improving these terms. Thus I am open to suggestions about the improvement of the apoptosis terms in general, but I'm not totally convinced of the need for the terms you suggest. The three terms you propose already have rough equivalents in the GO and perhaps should be added only as synonyms to those terms,
extrinsic pathway of apoptosis = induction of apoptosis by extracellular signals ; GO:0008624
Please also note the children of GO:0008624: --% induction of apoptosis by granzyme --% induction of apoptosis by hormones --% induction of apoptosis by ionic changes --% induction of apoptosis in response to chemical stimulus --% induction of apoptosis via death domain receptors
intrinsic pathway of apoptosis = induction of apoptosis by intracellular signals ; GO:0008629 --% DNA damage response, signal transduction resulting in induction of apoptosis + --% induction of apoptosis by oxidative stress
execution phase of apoptosis = apoptotic program ; GO:0008632 Please also note the children of GO:0008632 --< activation of pro-apoptotic gene products --< apoptotic cell clearance --< apoptotic mitochondrial changes --< apoptotic nuclear changes --< caspase activation --< cell structure disassembly during apoptosis
Also, I was concerned that none of the three references you gave actually referred by name to the "intrinsic pathway" or the "extrinsic pathway" of apoptosis. And I only found the phrase "execution phase" as part of a title of a reference used in PMID:12655297, not in the text itself. Consequently, we should cite additional or other literature for support of these terms. Reviews that I have found (PMID:16935409 and PMID: 16892092) that explicitly reference the extrinsic and intrinsic pathways of apoptosis, refer to them as signaling pathways, which furthers the rough equivalence of terms I give above.
However, another review (PMID:15725726) does refer explicitly to intrinsic and extrinsic pathways of apoptosis in very much the way you describe these pathways, as well as using the phrase "execution phase of apoptosis," and I would recommend this reference be use as support for these term names or synonyms. Nevertheless, whether these pathways are in fact signaling pathways remains open, and thus whether the terms you suggest are sufficiently distinct from the existing terms in the GO to warrant their inclusion remains open.
I would argue the introduction of new high level terms here would need to be done with an appropriate reorganization of the existing apoptosis terms. I think these high level terms may be of use, but we stand to confuse annotators and users if we fail to distinguish the new terms from the existing terms. Also, in such a complicated area as apoptosis, it is not sufficient simply to say "Some language useful for making definitions, and some literature references" and expect the GO editors to do all the heavy lifting. I would love to spend a month on the topic myself but have other obligations unfortunately. In general the best way to ensure rapid and correct term introduction in the GO is to provide definitions, complete parentage, including is_a parentage, good synonyms if possible, and good references.
Thanks,
Alex
Original comment by: addiehl
Now, the children of GO:0006915 'apoptosis' are mostly is-a children that describe apoptosis in a particular cell type or physiological state.
Could we have some part-of children to capture the phases of the generic apoptotic process:
apoptosis (GO:0006915) ... p extrinsic pathway of apoptosis (GO:ntr) ... p intrinsic pathway of apoptosis (GO:ntr) ... p execution phase of apoptosis (GO:ntr)
Some language useful for making definitions, and some literature references:
Known as the "death receptor pathway" the extrinsic or caspase 8/10 dependent pathway is activated by ligand binding. The "death receptors" are specialized cell-surface receptors including Fas/CD95, tumor necrosis factor-alpha (TNF-alpha) receptor 1, and two receptors, DR4 and DR5, that bind to the TNF-alpha related apoptosis-inducing ligand (TRAIL) (PMID:11048727)
The intrinsic (Bcl-2 inhibitable or mitochondrial) pathway of apoptosis functions in response to various types of intracellular stress including growth factor withdrawal, DNA damage, unfolding stresses in the endoplasmic reticulum and death receptor stimulation. Following the reception of stress signals, proapoptotic BCL-2 family proteins are activated and subsequently interact with and inactivate antiapoptotic BCL-2 proteins. This interaction leads to the destabilization of the mitochondrial membrane and release of apoptotic factors. These factors induce the caspase proteolytic cascade, chromatin condensation, and DNA fragmentation, ultimately leading to cell death (PMID:14634621)
In the execution phase of apoptosis, effector caspases cleave vital cellular proteins leading to the morphological changes that characterize apoptosis. These changes include destruction of the nucleus and other organelles, DNA fragmentation, chromatin condensation, cell shrinkage and cell detachment and membrane blebbing (PMID:12655297).
Peter D'E Reactome
Reported by: deustp01
Original Ticket: "geneontology/ontology-requests/4836":https://sourceforge.net/p/geneontology/ontology-requests/4836