scispace - formally typeset
Open AccessJournal ArticleDOI

mdm2 expression is induced by wild type p53 activity.

TLDR
It is suggested that the mdm2 gene is a target for activation by wt p53, and the induction of mDM2 expression by t p53 activity is at the mRNA level, suggesting a direct involvement of p53 in the process.
Abstract
We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 325 degrees C, a temperature at which ts-p53 possesses wild-type (wt)-like activities In the present study we show that p95 is a product of the mdm2 putative proto-oncogene The enhanced complex formation of mdm2 with ts-p53 in cells maintained at 325 degrees C is due to an elevation in total mdm2 protein levels following the temperature shift We further demonstrate that the induction of mdm2 expression by t p53 activity is at the mRNA level The induction occurs with very rapid kinetics and does not require de novo protein synthesis, suggesting a direct involvement of p53 in the process Based on these data and on recent findings implicating p53 as a transcription factor, we suggest that the mdm2 gene is a target for activation by wt p53 In view of the ability of mdm2 to act as a specific antagonist of p53 activity, this induction process may serve to tightly autoregulate p53 activity in living cells

read more

Citations
More filters
Journal ArticleDOI

WAF1, a potential mediator of p53 tumor suppression

TL;DR: A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
Journal ArticleDOI

Regulation of p53 stability by Mdm2

TL;DR: It is shown that interaction with Mdm2 can also result in a large reduction in p53 protein levels through enhanced proteasome-dependent degradation, which may contribute to the maintenance of low p53 concentrations in normal cells.
Journal ArticleDOI

Live or let die: the cell's response to p53

TL;DR: Understanding the complex mechanisms that regulate whether or not a cell dies in response to p53 will ultimately contribute to the development of therapeutic strategies to repair the apoptotic p53 response in cancers.
Journal ArticleDOI

Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain

TL;DR: It is demonstrated that p53 can be modified by acetylated both in vivo and in vitro, indicating a novel pathway for p53 activation and providing an example of an acetylation-mediated change in the function of a nonhistone regulatory protein.
Journal ArticleDOI

Cell cycle control and cancer

TL;DR: New insights in understanding of the cell cycle reveal how fidelity is normally achieved by the coordinated activity of cyclin-dependent kinases, checkpoint controls, and repair pathways and how this fidelity can be abrogated by specific genetic changes.
References
More filters
Journal ArticleDOI

p53 mutations in human cancers

TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
Journal ArticleDOI

p53, guardian of the genome

Journal Article

Participation of p53 Protein in the Cellular Response to DNA Damage

TL;DR: A role for the wild-type p53 protein in the inhibition of DNA synthesis that follows DNA damage is suggested and a new mechanism for how the loss of wild- type p53 might contribute to tumorigenesis is suggested.
Journal ArticleDOI

The p53 tumour suppressor gene

TL;DR: The cell cycle is composed of a series of steps which can be negatively or postively regulated by various factors, chief among the negative regulators is the p53 protein, which can lead to cancer.
Journal ArticleDOI

The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation

TL;DR: A product of the mdm-2 oncogene forms a tight complex with the p53 protein, and the mDM-2oncogene can inhibit p53-mediated transactivation.
Related Papers (5)