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ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage.
The p53 tumor suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. The rapid activation of p53 by ionizing radiation andExpand
The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications.
TLDR
The data strongly support the view of the PTEN/PI3K/AKT pathway as an important target for drug discovery. Expand
Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of apoptosis
TLDR
Evidence is provided that conflicting signals transduced by Akt and p53 are integrated via negative feedback between the two pathways, which suggests that depending on the balance of signals, p53-dependent downregulation of Akt may promote an irreversible commitment to apoptotic cell death, whereas effective recruitment ofAkt by appropriate survival signals may lead to activation of Mdm2, inactivation of p53, and eventually inhibition of p 53-dependent apoptosis. Expand
PTEN, more than the AKT pathway.
TLDR
AKT is more than a passive bridge toward PTEN tumorigenesis, since its expression not only allows but also enforces and accelerates the tumorigenic process in combination with other oncogenes. Expand
Physical and Functional Interaction between p53 and the Werner’s Syndrome Protein*
TLDR
It is reported here that the WRN protein can form a specific physical interaction with p53 that supports the existence of a cross-talk between WRN and p53, which may be important for maintaining genomic integrity and for preventing the accumulation of aberrations that can give rise to premature senescence and cancer. Expand
Regulation of p53
Abstract: The p53 tumor suppressor protein provides a major anti‐cancer defense mechanism, as underscored by the fact that the p53 gene is the most frequent target for genetic alterations in humanExpand
Excess β‐catenin promotes accumulation of transcriptionally active p53
β‐catenin is a multifunctional protein, acting both as a structural component of the cell adhesion machinery and as a transducer of extracellular signals. Deregulated β‐catenin protein expression,Expand
Excess β‐catenin promotes accumulation of transcriptionally active p53
TLDR
It is reported here that overexpression of β‐catenin results in accumulation of p53, apparently through interference with its proteolytic degradation, and is accompanied by augmented transcriptional activity of p 53 in the affected cells. Expand
Regulation of p53: intricate loops and delicate balances.
TLDR
This work discusses two autoregulatory feedback loops involving the beta-catenin protein and the other centering on the Akt/PKB protein kinase, where p53 exhibits very intricate interactions with other proteins known to play important roles in the determination of cell fate. Expand
PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti‐tumour activity
TLDR
The interactions of PM01183 with selected DNA molecules of defined sequence and its in vitro and in vivo cytotoxicity are characterized. Expand
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