Functional and physical communication between oncoproteins and tumor suppressors

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• 作者：E. V. Prochownik
• 关键词：CIN ; cyclins ; E2F ; Fanconi’ ; s anemia ; genomic instability ; MIN ; Myc ; peroxiredoxin ; p53 ; Rb
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2005
• 出版时间：November, 2005
• 年：2005
• 卷：62
• 期：21
• 页码：2438-2459
• 全文大小：319 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

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 (prdx1) 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.