p53 regulation by post-translational modification and nuclear retention in response to diverse stresses
Open Access
- 13 December 1999
- journal article
- review article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 18 (53), 7656-7665
- https://doi.org/10.1038/sj.onc.1203013
Abstract
P53 activation by diverse stresses involves post-translational modifications that alter its structure and result in its nuclear accumulation. We will discuss several unresolved topics regarding p53 regulation which are currently under investigation. DNA damage is perhaps the best-studied stress which activates p53, and recent data implicate phosphorylation at N-terminal serine residues as critical in this process. We discuss recent data regarding the potential kinases which modify p53 and the possible role of the resulting phosphorylation events. By contrast, much less is understood about agents which disrupt the mitotic spindle. The cell cycle phase, induction signal, and biochemical mechanism of the reversible arrest induced by microtubule disruption are currently under investigation. Finally, a key event in response to any genotoxic stress is the accumulation of p53 in the nucleus. The factors which determine the steady state level of p53 are starting to be elucidated, but the mechanisms responsible for nuclear accumulation and nuclear export remain controversial. We discuss new studies revealing a mechanism for nuclear retention of p53, and the potential contributions of MDM2 to this process.Keywords
This publication has 99 references indexed in Scilit:
- Prevention of mammalian DNA reduplication, following the release from the mitotic spindle checkpoint, requires p53 protein, but not p53-mediated transcriptional activityOncogene, 1998
- Regulation of p53 stability by Mdm2Nature, 1997
- Mdm2 promotes the rapid degradation of p53Nature, 1997
- p53 phosphorylation: Biochemical and functional consequencesLife Sciences, 1996
- Cellular accumulation of p53 protein: an independent prognostic factor in stage II breast cancerEuropean Journal of Cancer, 1994
- Microtubule dependency of p34cdc2 inactivation and mitotic exit in mammalian cells.The Journal of cell biology, 1994
- Allosteric activation of latent p53 tetramersCurrent Biology, 1994
- A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4Nature, 1993
- Phosphorylation on protein kinase C sites inhibits nuclear import of lamin B2.The Journal of cell biology, 1993
- S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule functionCell, 1991