An N-Terminal transformation-governing sequence of SV40 large T antigen contributes to the binding of both p110 and a second cellular protein, p120

Ewen, Mark E.; Ludlow, John W.; Marsilio, Erika; DeCaprio, James A.; Millikan, Robert C.; Cheng, Seng H.; Paucha, Eva; Livingston, David M.

doi:10.1016/0092-8674(89)90840-4

Cited by 232 publications

(151 citation statements)

References 68 publications

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“…The CR2 domain is necessary for T antigen's ability to complex with pRb, p107 and p130 (DeCaprio et al, 1988;Dyson et al, 1989;Ewen et al, 1989). Mutants 3213 and K1 both have substitutions at amino acid 107 but 3213 has a second substitution at amino acid 108.…”

Section: Activities Dependent Upon the Amino Terminusmentioning

confidence: 99%

“…Downstream of the J domain region is the CR2 domain (amino acids 102 ± 115) with homology to adenovirus E1A proteins, human papillomavirus type 16 E7 protein and polyoma virus T antigen. The CR2 is required for binding and sequestering the retinoblastoma susceptibility protein family of pocket proteins pRb, p107 and p130 (DeCaprio et al, 1988;Moran, 1988;Ewen et al, 1989). When T antigen binds these pocket proteins, they are unable to interact with, and repress the activity of, the transcription factor E2F, so E2F-dependent transcription proceeds and the cell enters the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

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Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen

et al. 1999

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We have used two di erent, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo ®broblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the amino terminal 176 amino acids which contain the J domain as well as the CR1 and CR2 domain required for binding and sequestering the RB family of pocket proteins. Moreover, we found that even though activities dependent only upon the amino terminus were su cient for immortalization they were unable to maintain it. This suggests that immortalization by these amino terminal functions requires either additional events or immortalization of a subset of cells within the heterogeneous rat embryo ®broblast population. We further found that an activity dependent upon amino acids 17 ± 27 which remove a portion of the CR1 domain and the predicted a-1 helix of the J domain was not necessary to maintain growth but was required for direct immortalization suggesting that at least one of the functions required initially was not required to maintain the immortal state. This represents the ®rst demonstration that some of the functions required for maintenance of the immortal state di er from those required for initiation of immortalization.

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Section: Activities Dependent Upon the Amino Terminusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen

et al. 1999

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“…As recently demonstrated, the viral antigens involved in cell transformation contain an amino acid motif (DLXCXE) that is highly conserved among the DNA tumour viruses (Moran, 1988;Figge et al, 1988). This motif has recently been shown to be essential to the transformation of rodent cells (Chen & Paucha, 1990;Barbosa et al, 1990) and to be involved in the binding of at least one tumour suppressor gene product (RB; Dyson et al, 1989;Ewen et al, 1989;Whyte et al, 1988;DeCaprio, 1988).…”

Section: Discussionmentioning

confidence: 99%

Frequent detection of bovine polyomavirus in commercial batches of calf serum by using the polymerase chain reaction

Schuurman

Steenis²,

Strien³

et al. 1991

Journal of General Virology

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Twenty commercial batches of calf serum, obtained from several suppliers, were tested for the presence of bovine polyomavirus (BPyV) DNA and antibodies against the virus. Using polymerase chain reaction (PCR) technology, BPyV DNA was detected in 70% of the batches; no BPyV was detected in any of the negative control samples. The specificity of the amplification reactions was proven by hybridization. PCR results were confirmed by virus isolation experiments performed with five PCR-positive and five PCRnegative serum batches. The results indicate that the use of calf serum to supplement tissue culture media involves a serious risk of contaminating cell cultures with BPyV. No correlation was observed between the presence or absence of anti-BPyV immunoglobulins and the detection of BPyV-specific DNA sequences in the serum batches.

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“…Whereas antibodies to pRb immunoprecipitated proteins in the range 110-114 kDa, only p110 co-immunoprecipitated with antibody to SV40 large T-antigen showing that it binds preferentially to the lower molecular weight hypophosphorylated form of pRb . The same amino-acid sequence element (LXCXE domain) of the large T-antigen protein also contributed to the formation of a complex with a second cellular protein with an apparent molecular of 120 kDa (Ewen et al, 1989). Presumably this second protein is pRb2 (see below).…”

Section: Interaction Of Sv40 Large T-antigen With Prb and Its Family mentioning

confidence: 99%

Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses

White

Khalili

2006

Oncogene

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The retinoblastoma gene product pRb and other members of the Rb family of pocket proteins have a central role in the regulation of cell cycle progression. Soon after its discovery, pRb was found to interact with the transforming oncoproteins of DNA tumor viruses and this led to rapid advances in our understanding of the mechanisms of viral transformation and cell cycle progression. DNA viruses of the polyomavirus family have small, circular, double-stranded DNA genomes contained within nonenveloped icosahedral capsids and are highly tumorigenic in experimental animals. At least three types of polyomavirus infect humans: JC virus (JCV), BK virus (BKV) and Simian Vacuolating virus-40. The early region of these viruses encodes the transforming proteins large T-antigen and small t-antigen, which are involved in viral replication and also promote transformation of cells in culture and oncogenesis in vivo. Binding of T-antigen to pRb promotes the activation of the E2F family of transcription factors, which induce the expression of cellular genes required for S phase. In the context of lytic infection, this cell cycle progression is necessary for viral replication because polyomaviruses rely on S phasespecific host factors for their DNA synthesis. In the context of cellular transformation and tumorigenesis, T-antigen/pRB interaction is an indispensable event.

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An N-Terminal transformation-governing sequence of SV40 large T antigen contributes to the binding of both p110 and a second cellular protein, p120

Cited by 232 publications

References 68 publications

Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen

Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen

Frequent detection of bovine polyomavirus in commercial batches of calf serum by using the polymerase chain reaction

Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses

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