Apoptosis and the Cell Cycle in Human Disease


The cell cycle and apoptosis are central gene‐regulated cellular pathways. A number of diseases evolve due to deregulation of these pathways.

Keywords: apoptosis; cell cycle; cancer; autoimmune disease; neurodegenerative disease

Figure 1.

Critical regulators and checkpoints of cell cycle progression. Cell cycle consists of G1, S, G2 and M phases as indicated with checkpoints in G1, G2 and M shown as horizontal T‐bars. Sequential activation of the indicated CDK‐Cyclin complexes drives the cell cycle (black arrows). Cell cycle progression can be blocked by negative regulators such as p16, pRb and p27/KIP1 or by exit from the cell cycle into G0 phase. Growth‐stimulatory signals can lead to re‐entry into the cell cycle. CDK: cyclin‐dependent kinase; pRb: retinoblastoma protein; KIP1: kinase inhibitor protein 1.

Figure 2.

Cellular pathways of apoptosis. FasL: Fas‐ligand; IAP: inhibitor of apoptosis; TNF: tumor necrosis factor; TRAIL: tumor necrosis factor‐related apoptosis‐inducing ligand. Inverted T is used to indicate inhibitory process while the arrow indicates activating process.



Chervonsky AV, Wang Y, Wong F, et al. (1997) The role of Fas in autoimmune diabetes. Cell 89: 17–24.

Evan GI and Vousden KH (2001) Proliferation, cell‐cycle and apoptosis in cancer. Nature 411: 342–348.

Malumbres M and Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nature Reviews 1: 222–231.

Rampino N, Yamamoto H, Ionov Y, et al. (1997) Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 275: 967–969.

Reed JC (2000) Warner‐Lambert/Parke‐Davis award lecture: mechanisms of apoptosis. American Journal of Pathology 157: 1415–1430.

Schmitt CA and Lowe SW (1999) Apoptosis and therapy. Journal of Pathology 187: 127–137.

Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267: 1456–1462.

Vogelstein B, Lane D and Levine A (2000) Surfing the p53 network. Nature 408: 307–310.

Wallace‐Brodeur RR and Lowe SW (1999) Clinical implications of p53 mutations. Cellular and Molecular Life Sciences 55: 64–75.

Weiss LM, Warnke RA, Sklar J and Cleary ML (1987) Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. New England Journal of Medicine 317: 1185–1189.

Further Reading

Bullock AN and Fersht AR (2001) Rescuing the function of mutant p53. Nature Reviews Genetics 1: 68–76.

Hengartner MO (2000) The biochemistry of apoptosis. Nature 407: 770–776.

Korsmeyer SJ and Zinkel SS (2001) Molecular biology of cancer: apoptosis. In: De Vita V, Hellman S and Rosenberg SA (eds.) Principles and Practice of Oncology, 6th edn, pp. 111–122. Philadelphia, PA: Lippincott, Williams & Wilkins Publishers.

Krammer PH (2000) CD95 deadly mission in the immune system. Nature 407: 789–795.

Nicholson DW (2000) From bench to clinic with apoptosis‐based therapeutic agents. Nature 407: 810–816.

Ponder BAJ (2001) Cancer genetics. Nature 17: 336–341.

Rich T, Allen RL and Wyllie AH (2000) Defying death after DNA damage. Nature 407: 777–783.

Shapiro GI and Harper JW (1999) Anticancer drug targets: cell cycle and checkpoint control. Journal of Clinical Investigation 104: 1645–1653.

Stassi GR and De Maria R (2002) Autoimmune thyroid disease: new models of cell death in autoimmunity. Nature Reviews Immunology 2: 195–204.

Yuan J and Yankner BA (2000) Apoptosis in the nervous system. Nature 407: 802–809.

Web Links

BAX (BCL2‐associated X protein); Locus ID: 581. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=581

BCL2 (B‐cell CLL/lymphoma 2); Locus ID: 596. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=596

TP53 (tumor protein p53 (Li‐Fraumeni syndrome)); Locus ID: 7157. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7157

BAX (BCL2‐associated X protein); MIM number: 600040. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?600040

BCL2 (B‐cell CLL/lymphoma 2); MIM number: 151430. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?151430

TP53 (tumor protein p53 (Li–Fraumeni syndrome)); MIM number: 191170. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?191170

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Sjöström, Johanna, and Mäkelä, Tomi(Sep 2006) Apoptosis and the Cell Cycle in Human Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006043]