Cellular proteins that are targetted by DNA tumor viruses for transformation

Abstract

Tumor suppressor genes are genetic loci whose loss is associated with tumor development. Because the inactivation of these genes is a key feature in the genesis of certain tumors, it has been postulated that the protein products of tumor suppressor genes function in the negative regulation of cell proliferation. Tumor suppressor genes have been identified by genetic analysis either as loci associated with an inherited predisposition to certain tumors or by mapping studies that demonstrate allelic loss (reduction to homozygosity or loss of heterozygosity) during tumor development. The retinoblastoma gene, RB-1, was originally identified and cloned through its association with childhood retinoblastoma and is one of the best studied examples of the tumor suppressor genes. It has been shown that RB protein is also a key target for transformation by the oncogenes of several small DNA tumor viruses. The E1A proteins of adenovirus, the large T antigens of polyomaviruses, and E7 proteins of papillomaviruses all bind to pRB. Genetic studies of all three viruses have shown that any mutation that destroys binding to pRB also destroys the ability of these proteins to transform cells, suggesting that interaction with the RB gene product is a key event in viral transformation. In addition to interacting with pRB, the adenovirus E1A proteins and the polyomavirus large T antigens also bind to other cellular proteins. One of these, a protein with a molecular weight 0f 107,000 daltons, 107K, binds to E1A and large T at the same amino acid region as pRB, suggesting that the 107K and pRB proteins may have structural similarities.(ABSTRACT TRUNCATED AT 250 WORDS)