Apoptosis Reference Genome Targets (Archived)

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Project leaders

Emily Dimmer

Justification (Impact and significance)

Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms.

Biochemical events lead to characteristic cell changes (morphology) and death. These changes include rounding-up of the cell, retraction of pseudopodes, plasma membrane blebbing, loss of cell membrane asymmetry and attachment,reduction of cellular volume (pyknosis), nuclear fragmentation (karyorrhexis), chromatin condensation, and chromosomal DNA fragmentation. Apoptosis produces cell fragments called apoptotic bodies that surrounding cells are able to engulf (often associated with phagocytes) and quickly remove before the contents of the cell can spill out onto surrounding cells and cause damage. Apoptosis is not synonymous with programmed cell death (PCD).

In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in an extensive variety of diseases. Excessive apoptosis causes atrophy, such as in ischemic damage, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer. [1],[2]

Notes for curators

Although the presence of active caspases and DNA fragmentation is helpful in identifying possible apoptosis, they should not be employed as an exclusive means to demonstrate this process as apototic cell death can occur without th DNA fragmentation or caspase activity.[1]

Cell death is frequently considered to be ‘caspase-dependent’ when it is suppressed by broad-spectrum caspase inhibitors such as N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk). As a word of caution, however, it should be noted that Z-VAD-fmk does not act on all caspases with an equal efficiency, and it also inhibits calpains and cathepsins, especially at high concentrations (>10 μM). Moreover, Z-VAD-fmk has been associated with several off-target effects that would result from the binding to cysteines on proteins other than cysteine proteases[1]

Range of species in which the pathway is found

Apoptosis Experts

Ontology status

Time frame of the project

Background reading

[1] [Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G; Nomenclature Committee on Cell Death 2009.Cell Death Differ. 2009 Jan;16(1):3-11. Epub 2008 Oct 10. http://www.ncbi.nlm.nih.gov/pubmed/18846107]

Highly recommended to read before starting curation; contains definitions of different types of cell death (apoptosis/necrosis/autophagic cell death/cornification, as described by the Nomenclature Committee on Cell Death.

[2] http://en.wikipedia.org/wiki/Apoptosis

Families to annotate (BATCH 1)

1. PTHR10454 - Caspases

PTHR10454:SF13: Caspase 1

- chicken ENTREZ=395764|UniProtKB=O42284

- human UniProtKB=P29466 (BHF priority (low); KRUK priority)

- mouse MGI=96544|UniProtKB=P29452

- rat RGD=2274|UniProtKB=P43527

PTHR10454:SF28 Caspase 1

- Drosophila FB=FBgn0010501|UniProtKB=O02002 FB=FBgn0019972|UniProtKB=O01382 FB=FBgn0028381|UniProtKB=Q9VET9

PTHR10454:SF30: Caspase 3

- rat RGD=2275|UniProtKB=P55213

- mouse MGI=MGI=107739|UniProtKB=P70677

- human UniProtKB=P42574

-chicken ENTREZ=395476|UniProtKB=O93417

-zebrafish ZDB-GENE-070607-1|UniProtKB=Q0PKX2 ZFIN=ZDB-GENE-011210-1|UniProtKB=Q98UI8

2. PTHR12768 (beclin-1) This has previously been a target, but many groups have not curated.

Human - UniProtKB=A8MW95

- UniProtKB=Q14457

S. Pombe -GeneDB_Spombe=SPAC20G8.10c|UniProtKB=P87117

s.cerevisiae SGD=S000006041|UniProtKB=Q02948

rat RGD=1563293|NCBI=XP_001059251 RGD=620190|UniProtKB=Q91XJ1

mouse MGI=MGI=2684950|NCBI=XP_129608 MGI=MGI=1891828|UniProtKB=O88597

C.elegans WB=WBGene00000247|UniProtKB=Q22592

Arabidopsis TAIR=locus=2076715|NCBI=NP_567116

chicken ENTREZ=420018|UniProtKB=Q5ZKS6

Drosophila FB=FBgn0010709|UniProtKB=Q9VCE1

3. PTHR15077 (FADD) rat RGD=628700|UniProtKB=Q8R2E7 mouse MGI=MGI=109324|UniProtKB=Q61160 human ENSEMBL=ENSG00000168040|UniProtKB=Q13158 (BHF priority low) chicken ENTREZ=423146|NCBI=XP_421073 ENTREZ=776859|NCBI=XP_001236356 drosophila FB=FBgn0038928|UniProtKB=Q9V3B4 Zebrafish ENSEMBL=ENSDARG00000068099|ENSEMBL=ENSDARP00000089060



(PTHR23257:SF93) - human UniProtKB=Q13546 (BHF priority (low) - rat RGD=1305538|NCBI=XP_345938 RGD=1310158|NCBI=XP_001065998 - mouse MGI=MGI=108212|UniProtKB=Q60855 - chicken ENTREZ=378921|UniProtKB=Q7ZZX8 - zebrafish ENSEMBL=ENSDARG00000006677|UniProtKB=Q0MSH9









Annotation targets/progress table (BATCH 1)