Simian virus 40 large T antigen's association with the CUL7 SCF complex contributes to cellular transformation.

Abstract

Simian virus 40 large T antigen (T Ag) is capable of immortalizing and transforming rodent cells. The transforming activity of T Ag is due in large part to perturbation of the tumor suppressor proteins p53 and the retinoblastoma (pRB) family members. Inactivation of these tumor suppressors may not be sufficient for T Ag-mediated cellular transformation. It has been shown that T Ag associates with an SCF-like complex that contains a member of the cullin family of E3 ubiquitin ligases, CUL7, as well as SKP1, RBX1, and an F-box protein, FBXW8. We identified T Ag residues 69 to 83 as required for T Ag binding to the CUL7 complex. We demonstrate that delta69-83 T Ag, while it lost its ability to associate with CUL7, retained binding to p53 and pRB family members. In the presence of CUL7, wild-type (WT) T Ag but not delta69-83 T Ag was able to induce proliferation of mouse embryo fibroblasts, an indication of cellular transformation. In contrast, WT and delta69-83 T Ag enabled mouse embryo fibroblasts to proliferate to similarly high densities in the absence of CUL7. Our data suggest that, in addition to p53 and the pRB family members, T Ag serves to bind to and inactivate the growth-suppressing properties of CUL7. In addition, these results imply that, at least in the presence of T Ag, CUL7 may function as a tumor suppressor.

• Authors: Jocelyn S Kasper, Hiroshi Kuwabara, Takehiro Arai, Syed Hamid Ali, James A DeCaprio
• Journal: Journal of virology (J Virol) Vol. 79 Issue 18 Pg. 11685-92 (Sep 2005) ISSN: 0022-538X [Print] United States
• PMID: 16140746 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Polyomavirus Transforming
• Multiprotein Complexes
• Tumor Suppressor Protein p53
• SKP Cullin F-Box Protein Ligases

Topics

• Animals
• Antigens, Polyomavirus Transforming (chemistry, genetics, physiology)
• Binding Sites
• Cell Division
• Cell Line
• Cell Transformation, Viral (genetics, physiology)
• HeLa Cells
• Humans
• Mice
• Mice, Knockout
• Multiprotein Complexes
• NIH 3T3 Cells
• SKP Cullin F-Box Protein Ligases (chemistry, deficiency, genetics, physiology)
• Simian virus 40 (genetics, immunology, pathogenicity, physiology)
• Tumor Suppressor Protein p53 (deficiency, genetics, metabolism)