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p53, the Cellular Gatekeeper for Growth and Division
  • A. Levine
  • Biology, Medicine
  • Cell
  • 7 February 1997
The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts. Expand
The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53
It is demonstrated that the E6 proteins of the oncogenic HPVs that bind p53 stimulate the degradation of p53, which results in selective degradation of cellular proteins such as p53 with negative regulatory functions provides a novel mechanism of action for dominant-acting oncoproteins. Expand
The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
A product of the mdm-2 oncogene forms a tight complex with the p53 protein, and the mDM-2oncogene can inhibit p53-mediated transactivation. Expand
Dynamics of the p53-Mdm2 feedback loop in individual cells
It is found that p53 was expressed in a series of discrete pulses after DNA damage, and it is suggested that the p53-Mdm2 feedback loop generates a 'digital' clock that releases well-timed quanta of p53 until damage is repaired or the cell dies. Expand
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-Residue transactivation domain peptide of p53 revealed that MDM 2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic α helix, supporting the hypothesis thatMDM2 inactivates p53 by concealing its transactivationdomain. Expand
The first 30 years of p53: growing ever more complex
Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus, and new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. Expand
Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
It is demonstrated that beclin 1 is a critical component of mammalian autophagy and a role forAutophagy in tumor suppression is established, and mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of Autophagy. Expand
Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study.
A simple mathematical model is presented suggesting that, under certain circumstances, oscillations in p53 and Mdm2 protein levels can emerge in response to a stress signal, and oscillations may allow cells to repair their DNA without risking the irreversible consequences of continuous excessive p53 activation. Expand
Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
The tumour-suppressor phosphatase with tensin homology (PTEN) is the most important negative regulator of the cell-survival signalling pathway initiated by phosphatidylinositol 3-kinase (PI3K), and deregulation of the PI3K–PTEN network occurs through other mechanisms. Expand
The p53-mdm-2 autoregulatory feedback loop.
The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm -2 gene can be regulated by the level of wild-type p53 protein. Expand