Functional and physical communication between oncoproteins and tumor suppressors.
The discovery of oncogenes (c-onc's) and tumor suppressors (TS's) has led to the concept that cancer arises from defects in each of these classes of genes or their products. More recently, it has been appreciated that c-onc and TS proteins often affect one another's functions. Within this context, I review the two classical TS's, p53 and the retinoblastoma protein, and the consequences of their inactivation. The various forms of genomic instability (GI) that underly the high mutation rates of transformed cells are then discussed. Particular emphasis is placed upon the concept that GI is not only an integral part of the transformed state but is a prerequisite. Increased oxidative DNA damage, and/or an inabiliy to repair it, can lead to GI. The review then discusses recent observations showing that loss of the TS protein peroxiredoxin 1 (prdx 1) and increased expression of the c-onc protein c-Myc, each leads to increased oxidative DNA damage. The critical nature of the c-onc-TS interaction is underscored by that occurring between prdx1 and c-Myc, with the former protein regulating the production of DNA-damaging reactive oxygen species by the latter. The intimate association between these proteins and others serves as a paradigm for the exquisite balancing act that c-onc's and TS's must maintain in order to properly control normal DNA replication and cellular proliferation while simultaneously minimizing the acquisition of potentially neoplastic mutations.
Prochownik
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Section of Hematology/Oncology, Children's Hospital of Pittsburgh, Rangos Research Center, Room 2100, 3460 Fifth Avenue, Pittsburgh, PA 15213, USA. procev@chp.edu
D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D015513:Oncogene Proteins; D025521:Tumor Suppressor Proteins