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
Apoptosis and the Cell Cycle in Human Disease
Johanna Sjöström, Helsinki University Hospital, Helsinki, Finland
Tomi Mäkelä, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Published online: September 2006
DOI: 10.1002/9780470015902.a0006043
|
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.
|
| References | |
| 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. | |
| book 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 | |
| ePath BAX (BCL2-associated X protein); Locus ID: 581. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=581 | |
| ePath BCL2 (B-cell CLL/lymphoma 2); Locus ID: 596. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=596 | |
| ePath TP53 (tumor protein p53 (Li-Fraumeni syndrome)); Locus ID: 7157. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7157 | |
| ePath BAX (BCL2-associated X protein); MIM number: 600040. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600040 | |
| ePath BCL2 (B-cell CLL/lymphoma 2); MIM number: 151430. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?151430 | |
| ePath TP53 (tumor protein p53 (Li–Fraumeni syndrome)); MIM number: 191170. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?191170 | |
