| First Author | Smogorzewska A | Year | 2002 |
| Journal | EMBO J | Volume | 21 |
| Issue | 16 | Pages | 4338-48 |
| PubMed ID | 12169636 | Mgi Jnum | J:78543 |
| Mgi Id | MGI:2385377 | Doi | 10.1093/emboj/cdf433 |
| Citation | Smogorzewska A, et al. (2002) Different telomere damage signaling pathways in human and mouse cells. EMBO J 21(16):4338-48 |
| abstractText | Programmed telomere shortening in human somatic cells is thought to act as a tumor suppressor pathway, limiting the replicative potential of developing tumor cells. Critically short human telomeres induce senescence either by activating p53 or by inducing the p16/RB pathway, and suppression of both pathways is required to suppress senescence of aged human cells. Here we report that removal of TRF2 from human telomeres and the ensuing de-protection of chromosome ends induced immediate premature senescence. Although the telomeric tracts remained intact, the TRF2(DeltaBDeltaM)-induced premature senescence was indistinguishable from replicative senescence and could be mediated by either the p53 or the p16/RB pathway. Telomere de-protection also induced a growth arrest and senescent morphology in mouse cells. However, in this setting the loss of p53 function was sufficient to completely abrogate the arrest, indicating that the p16/RB response to telomere dysfunction is not active in mouse cells. These findings reveal a fundamental difference in telomere damage signaling in human and mouse cells that bears on the use of mouse models for the telomere tumor suppressor pathway. |
