The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
Amplification of a gene encoding a p53-associated protein in human sarcomas
Results are consistent with the hypothesis thatMDM2 binds to p53, and that amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control, and this mechanism of tumorigenesis parallels that for virally-induced tumours.
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential
It is found that in cell lines containing inducible versions of alleles encoding the Pro72 and Arg72 variants, and in cells with endogenous p53, the Arg72 variant induces apoptosis markedly better than does the Pro 72 variant.
Mitochondrial p53 activates Bak and causes disruption of a Bak–Mcl1 complex
It is shown that, after cell stress, p53 interacts with the pro-apoptotic mitochondrial membrane protein Bak, which is consistent with a model in which p53 and Mcl1 have opposing effects on mitochondrial apoptosis by interacting with, and modulating the activity of, the death effector Bak.
A small molecule inhibitor of inducible heat shock protein 70.
Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a.
It is reported that trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs), abrogates the ability of p53 to repress the transcription of two genes that it negatively regulates, Map4 and stathmin, and p53 physically associates in vivo with HDACs.
Stabilization of the MDM2 Oncoprotein by Interaction with the Structurally Related MDMX Protein*
- Darcie A. Sharp, S. Kratowicz, Michael Sank, D. George
- BiologyJournal of Biological Chemistry
- 31 December 1999
The results obtained in these studies provide evidence that C-terminal RING finger domains, contained within both of these proteins, play an important role in mediating the association between MDM2 and MDMX.
Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line.
Analysis of amplified DNA sequences present in a tumorigenic mouse cell line provided evidence that a gene, mdm2, that is amplified more than 50‐fold in the 3T3DM cell line, induces tumorigenicity when experimentally overexpressed in NIH3T3 cells and in Rat2 cells.
Crystal Structure of the Stress-Inducible Human Heat Shock Protein 70 Substrate-Binding Domain in Complex with Peptide Substrate
The high-resolution structure of the substrate-bound-HSP70-SBD complex provides a molecular platform for the rational design of small molecule compounds that preferentially target this C-terminal domain, in order to modulate human HSP70 function.
Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene.
It is suggested that p53 can induce transcription from an internal promoter located within the mdm2 gene, which raises the possibility that, in addition to increasing the overall levels of mdm1 mRNA, wt p53 may also modulate the repertoire of mDM2 transcripts present within the cell.