Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence
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Ημερομηνία
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Exp Cell Res
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Normal cells display protective responses against oncogenes. Notably, oncogenic Ras triggers an irreversible proliferation arrest that is reminiscent of replicative senescence and that is considered a relevant tumor-suppressor mechanism. Here, we have used microarrayed filters to identify genes specifically upregulated in Ras-senescent human fibroblasts. Among the initial set of genes selected from the microarrays, we found the cell-cycle inhibitor p21(Cip1/Waf1), thus validating the potency of the screening to identify markers and mediators of Ras-senescence. A group of six genes, formed by those more highly upregulated during Ras-senescence, was analyzed in further detail to evaluate their specificity. In particular, we examined their expression in cells overexpressing Ras but rendered resistant to Ras-senescence by the viral oncoprotein E1a; also, we have studied their expression during replicative senescence, organismal aging, H(2)O(2)-induced senescence, and DNA damage. In this manner, we have identified a novel gene, RIS1 (for Ras-induced senescence 1), which is not upregulated in association to any of the above-mentioned processes, but exclusively during Ras-senescence. Furthermore, RIS1 is also upregulated by the transcriptional factor Ets2, which is a known mediator of Ras-induced senescence. Interestingly, RIS1 is located at chromosomal position 3p21.3 and, more specifically, it is included in a short segment of just 1 Mb previously defined by other investigators for its tumor-suppressor activity. In summary, we report the identification of a novel gene, RIS1, as a highly specific marker of Ras-induced senescence and a candidate tumor-suppressor gene.
Περιγραφή
Λέξεις-κλειδιά
Adenovirus E1A Proteins/metabolism/pharmacology, Adolescent, Adult, Aged, Aged, 80 and over, Cell Aging, Cell Division, Cell Line, Child, DNA Damage, *DNA-Binding Proteins, Female, Fibroblasts/cytology/drug effects, *Genes, Tumor Suppressor, Humans, Hydrogen Peroxide/pharmacology, Membrane Proteins, Middle Aged, Proto-Oncogene Protein c-ets-2, Proto-Oncogene Proteins/metabolism, *Repressor Proteins, Trans-Activators/metabolism, *Transcription Factors, *Transcriptional Activation, Tumor Suppressor Proteins/*genetics, Up-Regulation, ras Proteins/*metabolism/pharmacology
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/11822868
http://ac.els-cdn.com/S0014482701954345/1-s2.0-S0014482701954345-main.pdf?_tid=f1e4f1c724942279d52c19f7490a2c3e&acdnat=1332999248_c59a8ac9983c5733200a166f91441769
http://ac.els-cdn.com/S0014482701954345/1-s2.0-S0014482701954345-main.pdf?_tid=f1e4f1c724942279d52c19f7490a2c3e&acdnat=1332999248_c59a8ac9983c5733200a166f91441769
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής