Home > B. Cellular pathology > Apoptosis

Apoptosis

Wednesday 25 June 2003

GO:0006915

Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses.

Much of what happens during the demolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases (CASPs).

These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules.

Apoptosis molecular pathways

- caspases-dependent apoptosis pathway
- caspases-independent apoptosis pathway

Pathology of apoptosis

- pathology of caspases

  • caspase-9 (CASP9)

- pathology of fas and fas-ligand
- pathology of the bcl-2 pathway
- pathology of P53
- defects in the transmembrane tumor necrosis factor receptor 1 (TNF-R1): familial periodic fever syndrome
- mutations in the homologous receptor Fas (CD95; Apo-1) in malignant lymphomas, solid tumors and the autoimmune lymphoproliferative syndrome type I (ALPS I)
- mutation in the ligand for Fas (FASL; Fas ligand; CD95 ligand, Apo-1 ligand): systemic lupus erythematosus and lymphadenopathy
- Perforin (cytotoxic protein of T- and NK-cells for target cell killing): familial hemophagocytic lymphohistiocytosis
- Caspase 10 (CASP10) (caspase family of proteases): autoimmune lymphoproliferative syndrome type II (ALPS II)
- intracellular pro-apoptotic molecule bcl-10: mucosa-associated lymphoid tissue (MALT) lymphomas and various non-hematologic malignancies
- p53 (TP53), an executioner of DNA damage triggered apoptosis
- Bax (BAX), a pro-apoptotic molecule with the ability to perturb mitochondrial membrane integrity, are frequently mutated in malignant neoplasms
- anti-apoptotic proteins like bcl-2, cellular-inhibitor of apoptosis protein 2 (c-IAP2)
- neuronal apoptosis inhibitory protein 1 (NAIP1) are often altered in follicular lymphomas, MALT lymphomas and spinal muscular atrophy (SMA)

See also

- apoptosome
- apoptotic body
- inhibitors of apoptosis (IAPs)
- apoptosis in neurodegenerative disorders
- mitochondria-mediated apoptosis
- apoptotic hepatocytes (apoptotic bodies)
- apoptotic keratinocytes
- apoptotic engulfment
- anti-apoptosis therapy

Videos

- Apoptosis

- Apoptosis of osteoclasts

References

- Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2007 Dec 12; PMID: #18073771#

- Wodarz D, Komarova N. Can loss of apoptosis protect against cancer? Trends Genet. 2007 Mar 21; PMID: #17382429#

- Bremer E, van Dam G, Kroesen BJ, de Leij L, Helfrich W. Targeted induction of apoptosis for cancer therapy: current progress and prospects. Trends Mol Med. 2006 Aug;12(8):382-93. PMID: #16798087#

- Miller JB, Girgenrath M. The role of apoptosis in neuromuscular diseases and prospects for anti-apoptosis therapy. Trends Mol Med. 2006 Jun;12(6):279-86. PMID: #16650805#

- Moll UM, Wolff S, Speidel D, Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005 Dec;17(6):631-6. PMID: #16226451#

- Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005 Nov;5(11):876-85. PMID: #16239906#

- Perfettini JL, Roumier T, Kroemer G. Mitochondrial fusion and fission in the control of apoptosis. Trends Cell Biol. 2005 Apr;15(4):179-83. PMID: #15817372#

- Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 2005 Mar;5(3):231-7. PMID: #15738985#

- Senderowicz AM. Targeting cell cycle and apoptosis for the treatment of human malignancies. Curr Opin Cell Biol. 2004 Dec;16(6):670-8. PMID: #15530779#

- Edinger AL, Thompson CB. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004 Dec;16(6):663-9. PMID: #15530778#

- Abraham MC, Shaham S. Death without caspases, caspases without death. Trends Cell Biol. 2004 Apr;14(4):184-93. PMID: #15066636#

- Zahir N, Weaver VM. Death in the third dimension: apoptosis regulation and tissue architecture. Curr Opin Genet Dev. 2004 Feb;14(1):71-80. PMID: #15108808#

- Grimsley C, Ravichandran KS. Cues for apoptotic cell engulfment: eat-me, don’t eat-me and come-get-me signals. Trends Cell Biol. 2003 Dec;13(12):648-56. PMID: #14624843#

- Townson JL, Naumov GN, Chambers AF. The role of apoptosis in tumor progression and metastasis. Curr Mol Med. 2003 Nov;3(7):631-42. PMID: #14601637#

- Makin G, Dive C. Recent advances in understanding apoptosis: new therapeutic opportunities in cancer chemotherapy. Trends Mol Med. 2003 Jun;9(6):251-5. PMID: #12829013#

- Machamer CE. Golgi disassembly in apoptosis: cause or effect? Trends Cell Biol. 2003 Jun;13(6):279-81. PMID: #12791290#

- Mattson MP, Kroemer G. Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends Mol Med. 2003 May;9(5):196-205. PMID: #12763524#

- Ravagnan L, Roumier T, Kroemer G. Mitochondria, the killer organelles and their weapons. J Cell Physiol. 2002 Aug;192(2):131-7. PMID: #12115719#

- Cohen I, Castedo M, Kroemer G. Tantalizing Thanatos: unexpected links in death pathways. Trends Cell Biol. 2002 Jul;12(7):293-5. PMID: #12185842#

- Zhang J, Xu M. Apoptotic DNA fragmentation and tissue homeostasis. Trends Cell Biol. 2002 Feb ;12(2):84-9. PMID : #11849972#

- Kaufmann SH, Hengartner MO. Programmed cell death: alive and well in the new millennium. Trends Cell Biol. 2001 Dec;11(12):526-34. PMID: #11719060#

- Makin G, Dive C. Apoptosis and cancer chemotherapy. Trends Cell Biol. 2001 Nov;11(11):S22-6. PMID: #11684438#

- Mullauer L, Gruber P, Sebinger D, Buch J, Wohlfart S, Chott A. Mutations in apoptosis genes: a pathogenetic factor for human disease. Mutat Res. 2001 Jul;488(3):211-31. PMID: #11397650#

- Reed JC. Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med. 2001 Jul;7(7):314-9. PMID: #11425640#

- Huang P, Oliff A. Signaling pathways in apoptosis as potential targets for cancer therapy. Trends Cell Biol. 2001 Aug;11(8):343-8. PMID: #11489640#

- Mullauer L, Gruber P, Sebinger D, Buch J, Wohlfart S, Chott A.Mutations in apoptosis genes: a pathogenetic factor for human disease. Mutat Res 2001 Jul;488(3):211-31

- Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. 2000 Nov;1(2):120-9. PMID: #11253364#

- Beere HM, Green DR. Stress management - heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol. 2001 Jan;11(1):6-10. PMID: #11146277#

- Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 2000 Sep;10(9):369-77. PMID: #10932094#

- Webb SJ, et al: Apoptosis. An overview of the process and its relevance in disease. Adv Pharmacol 41:1, 1997.

- Kerr JF, et al: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239, 1972.

- Metzstein MM, Stanfield GM, Horvitz HR: Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet 14:410, 1998.

- Wyllie AH: Apoptosis: an overview. Br Med Bull 53:451, 1997.

- Strasser A, O’Connor L, Dixit VM: Apoptosis signaling. Annu Rev Biochem 69:217, 2000.

- McCarthy NJ, Evan GI: Methods for detecting and quantifying apoptosis. Curr Top Dev Biol 36:259, 1998.

- Vaux DL, Strasser A: The molecular biology of apoptosis. Proc Natl Acad Sci U S A 93:2239, 1996.