Mdm2: keeping p53 under control

Piette, Jacques; Neel, H. Bryan; Maréchal, Vincent

doi:10.1038/sj.onc.1201432

Cited by 245 publications

(195 citation statements)

References 67 publications

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“…Indeed the studies cited above may actually underestimate the frequency with which functional inactivation of p53 occurs in BL. Recent work performed in cell lines (Capoulade et al, 1998) has provided evidence for overexpression of mdm2, a protein which is a known inhibitor of p53 function (Piette et al, 1997). This observation clearly deserves further investigation in primary tumors.…”

Section: Burkitt's Lymphoma (Bl)mentioning

confidence: 88%

MYC oncogenes and human neoplastic disease

1999

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c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we ®rst summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite di erent roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in speci®c neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which signi®cant and con®rmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

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Section: Burkitt's Lymphoma (Bl)mentioning

confidence: 88%

MYC oncogenes and human neoplastic disease

1999

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“…Furthermore, recent studies have demonstrated additional mechanisms for p14ARF's function in controlling p53 activity independent of its ability to sequester Mdm2 in the nucleolus (Weber et al, 1999). As the cellular p53 protein level rises, p53 binds to the promoter of the Mdm2 gene, stimulating its transcrip-tion (p53-Mdm2 negative feedback loop; Piette et al, 1997). p14ARF is encoded by the INK4a gene locus, which also contains the gene for the cyclin dependent kinase inhibitor p16Ink4a (Serrano, 1997).…”

Section: Cell Cycle Control In Cancer Cellsmentioning

confidence: 99%

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

2002

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Accumulated knowledge in the molecular processes of tumour development combined with the availability of genetically modified viruses resemble the basis for new promising cancer therapeutics. The main advantages of employing replicationcompetent viruses are achievement of tumour selective killing and amplification of their oncolytic potential within the tumour mass. In this review, we describe the development of ONYX-015, one of the first and most advanced replication-competent viruses for cancer therapy. We discuss the molecular biology of this therapeutic approach and the interesting results obtained with this virus in clinical trials.

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“…It binds to the N-terminus of p53, represses its activities, mediates its nuclear export, and targets it to proteasome-mediated degradation. The Mdm2 gene is positively regulated by p53, thereby creating a negative feedback loop (reviewed by Momand and Zambetti, 1997;Piette et al, 1997a). Ser-20 of p53, a target for IR-induced phosphorylation , was recently implicated in the interaction of p53 with Mdm2.…”

Section: The G1/s Checkpoint and P53 Proteinmentioning

confidence: 99%

ATM: A mediator of multiple responses to genotoxic stress

1999

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The ATM protein kinase is the product of the gene responsible for the pleiotropic recessive disorder ataxiatelangiectasia. ATM-de®cient cells show enhanced sensitivity and greatly reduced responses to genotoxic agents that generate DNA double strand breaks (DSBs), such as ionizing radiation and radiomimetic chemicals, but exhibit normal responses to DNA adducts and base modi®cations induced by other agents. Therefore, DSBs are most likely the predominant signal for the activation of ATM-mediated pathways. Identi®cation of the ATM gene triggered extensive research aimed at elucidating the numerous functions of its large multifaceted protein product. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in the nucleus where it plays a central role in the very early stages of damage detection and serves as a master controller of cellular responses to DSBs. By activating key regulators of multiple signal transduction pathways, ATM mediates the e cient induction of a signaling network responsible for repair of the damage, and for cellular recovery and survival.

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Mdm2: keeping p53 under control

Cited by 245 publications

References 67 publications

MYC oncogenes and human neoplastic disease

MYC oncogenes and human neoplastic disease

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

ATM: A mediator of multiple responses to genotoxic stress

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