Novel Mechanism of Mammary Oncogenesis by Human Adenovirus Type 9
Abstract
The adenovirus E4 region-encoded open reading frame I (9ORFl) transforming protein is the major oncogenic determinant of human adenovirus type 9 (Ad9), a virus that generates exclusively estrogen-dependent mammary tumors in rats. We have found that 9ORFl complexes with four different cellular PDZ-domain proteins (MUPP 1, MAGI- 1, ZO-2, and DLG) and that these interactions are essential for its transforming activity. The fact that three of these 9ORFl-associated PDZ-domain proteins also complex with high-risk papillomavirus E6 oncoproteins provides further evidence that these cellular factors are relevant to transformation. Prompted by the knowledge that PDZ domain-containing proteins generally function in cell signaling, we recently showed that 9ORFl transforms cells, in part, by activating the phosphoinositide 3-kinase (PI 3-K)/protein kinase B (PKB) signaling pathway and, in addition, that this activity depends on the ability of 9ORFl to complex with its cellular PDZ-domain protein targets. We report here that the 9ORFl-associated protein MAGI-1 complexes with the tumor suppressor protein PTEN, a lipid phosphatase that antagonizes PI 3-K/PKB signaling in cells. We postulate that MAGI-1 may be an essential co-factor for PTEN and that activation of Pt 3-K/PKB signaling by E4-ORF 1 may be due in part to its ability to inactivate this PDZ protein in cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA387726
Entities
People
- Ronald Javier
Organizations
- Baylor College of Medicine