Apoptosis

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Aim

The aim of this project is to overhaul all the terms related to apoptosis in GO, mainly processes. Term phrasing and tree structures will be standardized, and new terms will be added with the aim of giving a broad coverage for all applicable species.


Background

APO-SYS is an EU-funded consortium of 23 partners, aiming at obtaining major progress in comprehension of apoptosis (and more generally cell death) in human diseases, by combining a series of systems biology approaches.

APO-SYS are funding a 9 month position at the EBI for a curator to improve the apoptosis term in GO and annotate papers to apoptotic GO terms, with recruitment beginning as soon as possible.

Apoptosis GO terms were discussed by members of the APO-SYS consortium at a meeting in Stockholm in 2009. The presentation is here: [1]


ISSUES AND IDEAS IN PROGRESS

Apoptosis overview.png


Definition of apoptosis ; GO:0006915

  • The first step is to decide where apoptosis begins and ends, and to improve the current GO definition of apoptosis ; GO:0006915. [2]
  • The current definition of apoptosis ; GO:0006915 covers ALL events INCLUDING the signaling events AND the physical death of a cell:

A form of programmed cell death that:

    • BEGINS when a cell receives internal or external signals that trigger the activity of proteolytic caspases,
    • PROCEEDS through a series of characteristic stages typically including rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), and plasma membrane blebbing (but maintenance of its integrity until the final stages of the process), and
    • ENDS with the death of the cell.
  • One idea is to limit 'apoptosis ; GO:0006915' to the death of a cell, and create upstream signaling events that regulate apoptosis. This is similar to how the signaling terms are structured in GO [3], and how Reactome view apoptosis: [4]


anti-apoptosis

  • We need to decide if the term 'anti-apoptosis ; GO:0006916' [5] is required, and if so, how it differs from 'negative regulation of apoptosis ; GO:0043066'.
  • What is 'positive regulation of anti-apoptosis ; GO:0045768'?
  • What is 'negative regulation of anti-apoptosis ; GO:0019987'?


Antiapoptosis2.png


To visualise these ideas, see Paola's presentation from the apoptosis call on May 12th 2011: [6].



Apoptosis Working Group

An apoptosis working group will be set up to discuss apoptosis in GO and the related problems.

Members of the apoptosis working group will be:

  • Samuel Kerrien
  • Emily Dimmer
  • Susan Tweedie
  • Rebecca Foulger
  • Paola Roncaglia
  • Ranjana Kishore
  • Marcus Chibucos

Apoptosis Content Meeting, June 1st 2011

  • An Apoptosis Content Meeting will be held at the EBI (Hinxton, UK) on Wednesday June 1st 2011.
  • The content meeting will be attended by apoptosis experts, GO editors and GO annotators, and will precede the 2-day APO-SYS Consortium Meeting (June 2nd and 3rd 2011).
  • Sam Kerrien (Intact) will organise and host the apoptosis content meeting.
  • The meeting will be funded by APO-SYS.
  • The presentation Paola gave at the Content Meeting can be found here [7].
  • The outcome from the apoptosis content meeting was presented on Friday June 3rd 2011, at the APO-SYS Consortium Meeting. Link here to Paola's summary [8].

Minutes of the content meeting are in the discussion part of this page.

Summary of Action Items from Apoptosis Content Meeting

• Change ‘apoptosis’ term name to ‘apoptotic process’

• Re-write definition of ‘apoptotic process’

• Work on the definition of cell death to include all types of cell death

• Make ‘apoptotic body’ a cellular component

• Make new term: ‘apoptotic signaling pathway’ and child terms intrinsic and extrinsic apoptotic signaling pathway

• Remove term ‘induction of apoptosis by extracellular signals’ and move child terms (with some re-working) under ‘intrinsic apoptotic signalling pathway’

• Change ‘induction of apoptosis by hormones’ to hormone-mediated signaling pathway

• Make new term ‘death receptor agonist activity’ as a child of ‘receptor agonist activity’

• Make new term ‘DISC assembly’ as a child of ‘apoptotic process’

• Email Zhivotovsky lab, what point does cross talk begin/end between intrinsic and extrinsic pathways

• Make new term ‘Death-induced signaling complex’

• Look into renaming of ‘activation of caspase activity’ to ‘activation of cysteine-type endopeptidase activity’

• RH: Look up Zhivotovsky lab papers for release of cytochrome c, MAC and PTP, email GI with specific questions

• Make new term ‘release of proteins from mitochondrion’

• Email Zhivotovsky lab. Mitochondrial pores – what is released? Does it depend on size of solutes or are certain molecules released?

• Check annotation examples for the existing term ‘release of matrix enzymes from mitochondria’, if need to keep this, change term name to ‘release of protein from mitochondrial matrix’

• Include in email to Zhivotovsky lab: ‘mitochondrial fragmentation’ can we put as a morphological change of apoptosis instead of a sub-process of apoptotic process?

• Contact yeast groups to check if yeast have apoptosomes

• GO:0071550 ‘death domain-mediated complex assembly’ appears to be redundant with new ‘DISC assembly’ term – merge terms

• Bring up at an annotation call: ‘protein complex assembly’ and the role of the components in assembly

• Revise use of ‘aggregation’ in protein complex terms

• Make new term ‘effector caspase activation’. But need another way to describe effector and initiator caspases within GO

• Obsolete ‘anti-apoptosis’ and add in regulation terms for the sub-processes of apoptotic process under ‘regulation of apoptotic process’

• move ‘negative regulation of survival gene product expression’ to under ‘positive regulation of apoptosis’ and move ‘positive regulation of survival gene product expression’ to under ‘negative regulation of apoptosis’

• Obsolete ‘positive regulation of anti-apoptosis’ and ‘negative regulation of anti-apoptosis’

• GI: Need to check whether ‘Phosphatidylserine exposure on apoptotic cell surface’ this is a terminal event or whether the cell can recover after this

• make new term ‘execution phase of apoptosis’

• make new terms ‘extrinsic apoptotic signaling pathway via apoptotic mitochondrial change’ and ‘extrinsic apoptotic signaling pathway via direct activation of effector caspase’ as child terms of ‘extrinsic apoptotic signaling pathway’

• consult apoptosis community on what to call apoptosis-like process that is independent of caspase

• [Paola: also look at GO:0008303 caspase complex and its annotations]

Apoptosis call, May 12th 2011

A call was held with GO curators, editors and apoptosis experts to highlight what needs to be done at the Apoptosis workshop in June.

The presentation Paola gave at the call can be found here [9].

The presentation includes:

  • A brief introduction to GO.
  • A summary of the current arrangement of apoptosis GO terms.
  • Problems identified with the current GO terms and their arrangement.
  • Possible ways to proceed with improving the apoptosis node.

Minutes of the call are in the discussion part of this page.

Apoptosis call, July 20th 2011

A call was held with GO curators, editors and apoptosis experts to follow-up on work done at the Apoptosis workshop in June.

The presentation that was referred to during the call can be found here File:Apoptosis call 20 07 2011.pdf.

Minutes of the call are in the discussion part of this wiki.

APO-SYS consortium wrap-up meeting, September 13th 2011

A presentation describing the re-structuration work of the ontology was given to the APO-SYS domain experts File:110913 ApoSys PPM.ppt.

The experts were asked to have an additional content meeting in the EBI, Hinxton, at some point around October-November; but the idea was finally dismissed due to incompatibility of agendas. In its place, it was decided that a document hoding requests and updates would be periodically exchanged between the experts and the GO annotation and editorial teams.

Annotation Targets

Please see the Reference Genome Apoptosis project page for details on targets currently selected for curation by GO Consortium annotation groups.

SF items

Websites and Resources

APO-SYS Consortium

Apoptosis Journal

Apoptosis Curation Manual

Relevant Papers

REVIEWS

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Galluzzi et al. Cell Death Differ. 2011 Jul 15 PMID:21760595

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Kroemer et al. Cell Death Differ. 2009 Jan;16(1):3-11 PMID:18846107

Four deaths and a funeral: from caspases to alternative mechanisms. Leist M, Jäättelä M. Nat Rev Mol Cell Biol. 2001 Aug;2(8):589-98. PMID:11483992

Cell death: critical control points. Danial NN, Korsmeyer SJ. Cell. 2004;116(2):205-19. PMID:14744432

The BCL-2 protein family: opposing activities that mediate cell death. Youle RJ, Strasser A. Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59. PMID:18097445

Alternative cell death mechanisms in development and beyond. Yuan J, Kroemer G. Genes Dev. 2010; 24(23):2592-602. PMID:21123646

Caspase-dependent and caspase-independent cell death pathways in yeast. Madeo F, Carmona-Gutierrez D, Ring J, Büttner S, Eisenberg T, Kroemer G. Biochem Biophys Res Commun. 2009;382(2):227-31. PMID:19250922

No death without life: vital functions of apoptotic effectors. Galluzzi L, Joza N, Tasdemir E, Maiuri MC, Hengartner M, Abrams JM, Tavernarakis N, Penninger J, Madeo F, Kroemer G. Cell Death Differ. 2008;15(7):1113-23. Epub 2008 PMID:18309324

Systems biology of apoptosis signaling networks. Lavrik IN. Curr Opin Biotechnol. 2010 Aug;21(4):551-5. PMID:20674332

From sentencing to execution--the processes of apoptosis. Moffitt KL, Martin SL, Walker B. J Pharm Pharmacol. 2010 May;62(5):547-62. PMID: 20609056

Where, O death, is thy sting?. A brief review of apoptosis biology. Wyllie AH. Mol Neurobiol. 2010 Aug;42(1):4-9. PMID:20552413

Existing apoptosis structure

This is a snapshot of where 'apoptosis ; GO:0006915' and its children are currently housed in GO: February 9th 2011

An Excel spreadsheet showing all of the apoptosis-related terms currently in the GO (February 2011)

A QuickGO chart view of the main structure of apoptosis terms currently in the GO (February 2011).

  • N.B. this chart does not contain all apoptosis-related terms, please see the Excel spreadsheet above for this list.
  • N.B. Click on the chart to zoom in
  • Apoptosis Chart.png