Caretakers and Gatekeepers

Antonio Russo, University of Palermo, Palermo, Italy
Manuela Migliavacca, University of Palermo, Palermo, Italy
Ines Zanna, University of Palermo, Palermo, Italy
Marcella Macaluso, Temple University, Philadelphia, Pennsylvania, USA
Nicola Gebbia, University of Palermo, Palermo, Italy
Viviana Bazan, University of Palermo, Palermo, Italy

Published online: January 2006

DOI: 10.1038/npg.els.0006048

It has now been generally accepted that the genes responsible for familial cancer syndromes can be divided into two categories, known as caretakers and gatekeepers. Caretakers are genes that control the maintenance of the genetic information integrity in each cell while gatekeepers are those genes which directly regulate tumor growth, codifying for proteins which either stimulate or inhibit proliferation, differentiation or apoptosis.

Keywords: gatekeeper genes; caretaker genes; tumor suppressor genes; cell cycle; hereditary syndromes

Figure 1. Caretaker and gatekeeper pathways.
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 References
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 Further Reading
    Bellacosa A (2001) Functional interactions and signaling properties of mammalian DNA mismatch repair proteins. Cell Death and Differentiation 8: 1076–1092.
    Berneburg M and Lehmann AR (2001) Xeroderma pigmentosum and related disorders: defects in DNA repair and transcription. Advances in Genetics 43: 71–102.
    book Kinzler KW and Vogelstein B (2002) "Familial cancer syndromes: the role of caretakers and gatekeepers". In: Kinzler KW and Vogelstein B (eds.) The Genetic Basis of Human Cancer, pp. 209–210. New York: McGraw-Hill
    MacLeod K (2000) Tumor supressor genes. Current Opinion in Genetics and Development 10: 81–93.
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    Russo A, Zanna I, Tubiolo C, et al. (2000) Hereditary common cancers: molecular and clinical genetics. Anticancer Research 20: 4841–4852.
    Schwab M, Claas A and Savelyeva L (2002) BRCA2: a genetic risk factor for breast cancer. Cancer Letters 175: 1–8.
    Torres J, Navarro S, Rogla I, et al. (2001) Heterogeneous lack of expression of the tumour suppressor PTEN protein in human neoplastic tissue. European Journal of Cancer 37: 114–121.
 Web Links
    ePath Genew: Human Gene Nomenclature Database. Gives the full names and approved symbols for human genes with links to further information http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl
    ePath Adenomatosis polyposis coli (APC); Locus ID: 324. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=324
    ePath Ataxia telangiectasia mutated (includes complementation groups A, C and D) (ATM); Locus ID: 472. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=472
    ePath Phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN); Locus ID: 5728. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5728
    ePath Retinoblastoma 1 (including osteosarcoma) (RB1); Locus ID: 5925. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5925
    ePath Tumor protein p53 (Li–Fraumeni syndrome) (TP53); Locus ID: 7157. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7157
    ePath Adenomatosis polyposis coli (APC); MIM number: 175100. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?175100
    ePath Ataxia telangiectasia mutated (includes complementation groups A, C and D) (ATM); MIM number: 208900. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?208900
    ePath Phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN); MIM number: 601728. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601728
    ePath Retinoblastoma 1 (including osteosarcoma) (RB1); MIM number: 180200. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?180200
    ePath Tumor protein p53 (Li-Fraumeni syndrome) (TP53); MIM number: 191170. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?191170

Related Sub-Topics:

Intracellular and Extracellular Signalling | Cell Biology of Cancer | Cell Cycle | Cell Death and Cellular Senescence | Molecular Genetics of Common and Complex Disease | Cancer Genetics | Epigenetics and Disease | Gene Expression Profiling of Genetic Disease | Transcriptional Regulation | Mechanisms of Cell Death, Senescence and Metabolism
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Article Title: Caretakers and Gatekeepers
 
How to Cite close
Russo, Antonio, Migliavacca, Manuela, Zanna, Ines, Macaluso, Marcella, Gebbia, Nicola, and Bazan, Viviana(Jan 2006) Caretakers and Gatekeepers. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006048]