The T/t common region of simian virus 40 large T antigen contains a distinct transformation-governing sequence

Abstract

Simian virus 40 large T antigen (T) can transform cultured cells, but the mechanisms by which it functions are not entirely understood. Several lines of evidence have suggested that the amino-terminal 130 residues of T may be sufficient to confer the transforming capability. Oligonucleotide-directed mutagenesis was used to generate a series of deletion and substitution mutants within the amino-terminal 82 residues of T, the segment which is shared with simian virus 40 small t antigen (t). Results of stability and transformation assays of these mutants strongly suggest that the 1-to-82 region of T contains sequences which govern T transforming activity and affect in vivo stability. Instability and a defect in transforming activity could be separated from one another genetically. Thus, the 1-to-82 region appears to contain a specific region that contributes to the transforming function of the protein. This segment operates by means other than the simple binding of pRb and/or p107.

Probing formation of cargo/importin‐α transport complexes in plant cells using a pathogen effector

“…This could either be due to a second NLS in the HaRxL106DC sequence, or due to elevated passive diffusion of the RFP-HaRxL106DC construct (predicted molecular weight 51.3 versus 57.8 kDa for RFP-HaRxL106). To test for presence of an additional NLS we replaced the two clusters of basic amino acids in the predicted bipartite NLS of HaRxL106 by the amino acid sequence NAAIRS, which is unlikely to interfere with protein secondary structure (Wilson et al, 1985;Marsilio et al, 1991). This RFP-HaRxL106 NAAIRS1+2 fusion protein was more efficiently excluded from nuclei than the RFP-HaRxL106DC fusion (Figure 1a), suggesting that the residual nuclear localization of the latter construct is due to passive diffusion into nuclei.…”

Retinoblastoma protein family in cell cycle and cancer: A review

“…pRb also interacts specifically with the SV40 large T [DeCaprio et al, 19881 and with the human papillomavirus E7 oncoproteins [Dyson et al, 1989bl. Like pRb, p107 and pRb2/p130 also bind to key transforming sequences of these viral oncoproteins [Dyson et al, 1989a;Ewen et al, 1991;Marsilio et al, 1991;Giordano et al, 1991;Dyson et al, 1992;Mayol et al, 1993;Ludlow and Skuse, 19951. These viral oncoproteins seem designed t o actively compete with the E2F family members in binding to the pocket proteins. ElA, for example, is able to dissociate E2F-1 from the pocket of pRb, despite the fact that the pocket segments responsible for the binding of E1A end E2F-1 may be different [Fattaey et al, 19931.…”

Association of p300 and CBP with Simian Virus 40 Large T Antigen

“…Extensive analyses of T mutants revealed the existence of two additional regions which contribute to its mitogenic function (12,40,41,43,47,49,50,62). The first is located in the N-terminal 82 residues and has been postulated to bind p300.…”

“…T molecules bearing mutations in the first 82 amino-terminal residues often display several defects. In addition to their impaired mitogenic potential, they are also defective in transforming cultured cells (40,49,62), despite their residual ability to interact with Rb family members and with p53. In transgenic mice, such a T mutant induced tumors in a subset of tissues in which it was expressed and it did so at a reduced frequency compared with wild-type (wt) T (50).…”