Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence
Φόρτωση...
Ημερομηνία
Συγγραφείς
Barradas, M.
Gonos, E. S.
Zebedee, Z.
Kolettas, E.
Petropoulou, C.
Delgado, M. D.
Leon, J.
Hara, E.
Serrano, M.
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