[The role of telomere-binding proteins in carcinogenesis].
Normal somatic cells have a defined number of divisions, a limited capacity to proliferative. The telomeres, sequences of TTAGGG repeats at the ends of chromosomes, are considered the direct responsible of the control of the cellular cycle. In fact, the progressive shortening of telomere length at each cellular division, causes the entrance of the cells in a phase of senescence and than apoptosis. The maintenance of the length of telomeres is carried out through: the telomerase, a DNA polymerase reverse transcriptase that extends sequence TTAGGG repeats, or the alternative lengthening of telomeres (ALT), between which the adaptive mechanisms, inactivation of TRF1, a protein bound to the telomeres with the functions of inhibiting the telomerase activity and Tankirase-PARP, an enzymatic complex that ADP-ribosylate TRF1 and reduce its binding to DNA. The alteration of the mechanism of maintenance of the telomeres length (Telomerase, TRF1, Tankirase-PARP) may represent a first step toward the cell immortalization and cancerogenesis. Together with the alteration of the control mechanisms of the telomere length, also the cell genic contest should be considered. In fact, the oncogene activation and/or oncosuppressor gene inactivation (p53, Rb, ras) may allow or reduce the cancerogenesis. From this point of view, the telomerase, the TRF1, Tanchirase-PARP and other proteins involved in telomere length could be, in a near future, used as new indicators of prognosis and as markers for new anti-cancer therapies.
Unità Operativa di Oncologia Medica, Policlinico Universitario G. Martino, Università degli Studi, Messina. aragona@sirio-oncology.it/marcello.aragona@unime.it
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D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000502:physiology*; D035321:Telomeric Repeat Binding Protein 1
D004268:DNA-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase