The J domain of Simian virus 40 large T antigen is required to functionally inactivate RB family proteins

被引:131
作者
Zalvide, J
Stubdal, H
DeCaprio, JA
机构
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
D O I
10.1128/MCB.18.3.1408
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transformation by simian virus 30 large T antigen (TAg) is dependent on the inactivation of cellular tumor suppressors. Transformation minimally requires the following three domains: (i) a C-terminal domain that mediates binding to p53; (ii) the LXCSE domain (residues 103 to 107), necessary for binding to the retinoblastoma tumor suppressor protein, pRB, and the related p107 and p130; and (iii) an N-terminal domain that is homologous to the J domain of DnaJ molecular chaperone proteins. We have previously demonstrated that the N-terminal J domain of TAg affects the RE-related proteins by perturbing the phosphorylation status of p107 and p130 and promoting the degradation of p130 and that this domain is required for transformation of cells that express either p107 or p130, In this work, we demonstrate that the J domain of TAg is required to inactivate the ability of each member of the pRB family to induce a G(1) arrest in Saos-2 cells. Furthermore, the J domain is required to override the repression of E2F activity mediated by p130 and pRB and to disrupt p130-E2F DNA binding complexes, These results imply that while the LXCSE domain serves as a binding site for the RE-related proteins, the J domain plays an important role in inactivating their function.
引用
收藏
页码:1408 / 1415
页数:8
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