Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Export

@article{citeulike:1178384, abstract = {Cellular senescence can be triggered by telomere shortening as well as a variety of stresses and signaling imbalances. We used multiparameter single-cell detection methods to investigate upstream signaling pathways and ensuing cell cycle checkpoint responses in human fibroblasts. Telomeric foci containing multiple DNA damage response factors were assembled in a subset of senescent cells and signaled through ATM to p53, upregulating p21 and causing G1 phase arrest. Inhibition of ATM expression or activity resulted in cell cycle reentry, indicating that stable arrest requires continuous signaling. ATR kinase appears to play a minor role in normal cells but in the absence of ATM elicited a delayed G2 phase arrest. These pathways do not affect expression of p16, which was upregulated in a telomere- and DNA damage-independent manner in a subset of cells. Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals.}, address = {Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.}, author = {Herbig, Utz and Jobling, Wendy A. and Chen, Benjamin P. and Chen, David J. and Sedivy, John M.}, citeulike-article-id = {1178384}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/15149599}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=15149599}, day = {21}, issn = {1097-2765}, journal = {Molecular cell}, keywords = {atm, p53, senescence}, month = {May}, number = {4}, pages = {501--513}, posted-at = {2007-03-20 20:31:01}, priority = {2}, title = {Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a).}, url = {http://view.ncbi.nlm.nih.gov/pubmed/15149599}, volume = {14}, year = {2004} }

TY - JOUR ID - citeulike:1178384 L3 - citeulike-article-id:1178384 N2 - Cellular senescence can be triggered by telomere shortening as well as a variety of stresses and signaling imbalances. We used multiparameter single-cell detection methods to investigate upstream signaling pathways and ensuing cell cycle checkpoint responses in human fibroblasts. Telomeric foci containing multiple DNA damage response factors were assembled in a subset of senescent cells and signaled through ATM to p53, upregulating p21 and causing G1 phase arrest. Inhibition of ATM expression or activity resulted in cell cycle reentry, indicating that stable arrest requires continuous signaling. ATR kinase appears to play a minor role in normal cells but in the absence of ATM elicited a delayed G2 phase arrest. These pathways do not affect expression of p16, which was upregulated in a telomere- and DNA damage-independent manner in a subset of cells. Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals. IS - 4 JF - Molecular cell SN - 1097-2765 AD - Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA. EP - 513 TI - Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). VL - 14 SP - 501 KW - atm KW - p53 KW - senescence AU - Herbig, Utz AU - Jobling, Wendy AU - Chen, Benjamin AU - Chen, David AU - Sedivy, John PY - 2004/05/21/ UR - http://view.ncbi.nlm.nih.gov/pubmed/15149599 ER -