Crosstalk of the mitotic spindle assembly checkpoint with p53 to prevent polyploidy. Export

@article{citeulike:1094061, abstract = {Treatment of cells with microtubule inhibitors results in activation of the mitotic spindle assembly checkpoint, leading to mitotic arrest before anaphase. Upon prolonged treatment, however, cells can adapt and exit mitosis aberrantly, resulting in the occurrence of tetraploid cells in G1. Those cells subsequently arrest in postmitotic G1 due to the activation of a p53-dependent G1 checkpoint. Failure of the G1 checkpoint leads to endoreduplication and further polyploidization. Using HCT116 and isogenic p53-deficient or spindle checkpoint compromised derivatives, we show here that not only p53 but also a functional spindle assembly checkpoint is required for postmitotic G1 checkpoint function. During transient mitotic arrest, p53 stabilization and activation is triggered by a pathway independent of ATM/ATR, Chk1 and Chk2. We further show that a prolonged spindle checkpoint-mediated mitotic arrest is required for proper postmitotic G1 checkpoint function. In addition, we demonstrate that polyploid cells are inhibited to re-enter mitosis by an additional checkpoint acting in G2. Thus, during a normal cell cycle, polyploidization and subsequent aneuploidization is prevented by the function of the mitotic spindle checkpoint, a p53-dependent G1 checkpoint and an additional G2 checkpoint.}, address = {Institute for Molecular Biology and Tumor Research, Philipps University Marburg, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany.}, author = {Vogel, C. and Kienitz, A. and Hofmann, I. and M\"{u}ller, R. and Bastians, H.}, citeulike-article-id = {1094061}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/sj.onc.1207860}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15286707}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15286707}, day = {9}, doi = {10.1038/sj.onc.1207860}, issn = {0950-9232}, journal = {Oncogene}, keywords = {aneuploidy, arrest, death, mitotic, p53, polyploidy, spindlecheckpoint, tetraploidy}, month = {September}, number = {41}, pages = {6845--6853}, posted-at = {2009-02-27 18:37:38}, priority = {2}, title = {Crosstalk of the mitotic spindle assembly checkpoint with p53 to prevent polyploidy.}, url = {http://dx.doi.org/10.1038/sj.onc.1207860}, volume = {23}, year = {2004} }

TY - JOUR ID - citeulike:1094061 L3 - citeulike-article-id:1094061 N2 - Treatment of cells with microtubule inhibitors results in activation of the mitotic spindle assembly checkpoint, leading to mitotic arrest before anaphase. Upon prolonged treatment, however, cells can adapt and exit mitosis aberrantly, resulting in the occurrence of tetraploid cells in G1. Those cells subsequently arrest in postmitotic G1 due to the activation of a p53-dependent G1 checkpoint. Failure of the G1 checkpoint leads to endoreduplication and further polyploidization. Using HCT116 and isogenic p53-deficient or spindle checkpoint compromised derivatives, we show here that not only p53 but also a functional spindle assembly checkpoint is required for postmitotic G1 checkpoint function. During transient mitotic arrest, p53 stabilization and activation is triggered by a pathway independent of ATM/ATR, Chk1 and Chk2. We further show that a prolonged spindle checkpoint-mediated mitotic arrest is required for proper postmitotic G1 checkpoint function. In addition, we demonstrate that polyploid cells are inhibited to re-enter mitosis by an additional checkpoint acting in G2. Thus, during a normal cell cycle, polyploidization and subsequent aneuploidization is prevented by the function of the mitotic spindle checkpoint, a p53-dependent G1 checkpoint and an additional G2 checkpoint. IS - 41 JF - Oncogene SN - 0950-9232 AD - Institute for Molecular Biology and Tumor Research, Philipps University Marburg, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany. EP - 6853 TI - Crosstalk of the mitotic spindle assembly checkpoint with p53 to prevent polyploidy. VL - 23 SP - 6845 KW - aneuploidy KW - arrest KW - death KW - mitotic KW - p53 KW - polyploidy KW - spindlecheckpoint KW - tetraploidy AU - Vogel, C AU - Kienitz, A AU - Hofmann, I AU - Müller, R AU - Bastians, H PY - 2004/09/09/ UR - http://dx.doi.org/10.1038/sj.onc.1207860 ER -