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The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo

Lookup NU author(s): Dr Gabriele Saretzki

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Abstract

Telomere dysfunction induces two types of cellular response: cellular senescence and apoptosis. We analysed the extent to which the cellular level of telomere dysfunction and p53 gene status affect these cellular responses in mouse liver using the experimental system of TRF2 inhibition by a dominant-negative version of the protein (TRF2ΔBΔM). We show that the level of telomere dysfunction correlates with the level of TRF2ΔBΔM protein expression resulting in chromosomal fusions, aberrant mitotic figures and aneuploidy of liver cells. These alterations provoked p53-independent apoptosis, but a strictly p53-dependent senescence response in distinct populations of mouse liver cells depending on the cellular level of TRF2ΔBΔM expression. Apoptosis was associated with higher expression of TRF2ΔBΔM, whereas cellular senescence was associated with low levels of TRF2ΔBΔM expression. Our data provide experimental evidence that induction of senescence or apoptosis in vivo depends on the cellular level of telomere dysfunction and differentially on p53 gene function. ©2005 European Molecular Biology Organization.


Publication metadata

Author(s): Lechel A, Satyanarayana A, Ju Z, Plentz RR, Schaetzlein S, Rudolph C, Wilkens L, Wiemann SU, Saretzki G, Malek NP, Manns MP, Buer J, Rudolph KL

Publication type: Article

Publication status: Published

Journal: EMBO Reports

Year: 2005

Volume: 6

Issue: 3

Pages: 275-281

Print publication date: 01/03/2005

ISSN (print): 1469-221X

ISSN (electronic): 1469-3178

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.embor.7400352

DOI: 10.1038/sj.embor.7400352

PubMed id: 15723042


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