scholarly journals Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen

2012 ◽  
Vol 518 (2) ◽  
pp. 111-118 ◽  
Author(s):  
Christina K. Williams ◽  
Sivaraja Vaithiyalingam ◽  
Michal Hammel ◽  
James Pipas ◽  
Walter J. Chazin
Keyword(s):  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
J Domain ◽  
Pocket Domain

scholarly journals Species-Specific Elements in the Large T-Antigen J Domain Are Required for Cellular Transformation and DNA Replication by Simian Virus 40

2000 ◽  
Vol 20 (15) ◽  
pp. 5749-5757 ◽  
Author(s):  
Christopher S. Sullivan ◽  
James D. Tremblay ◽  
Sheara W. Fewell ◽  
John A. Lewis ◽  
Jeffrey L. Brodsky ◽  
...  
Keyword(s):  
Dna Replication ◽  
Jc Virus ◽  
Simian Virus 40 ◽  
Cellular Transformation ◽  
Simian Virus ◽  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
J Domain ◽  
Species Specific

ABSTRACT The J domain of simian virus 40 (SV40) large T antigen is required for efficient DNA replication and transformation. Despite previous reports demonstrating the promiscuity of J domains in heterologous systems, results presented here show the requirement for specific J-domain sequences in SV40 large-T-antigen-mediated activities. In particular, chimeric-T-antigen constructs in which the SV40 T-antigen J domain was replaced with that from the yeast Ydj1p or Escherichia coli DnaJ proteins failed to replicate in BSC40 cells and did not transform REF52 cells. However, T antigen containing the JC virus J domain was functional in these assays, although it was less efficient than the wild type. The inability of some large-T-antigen chimeras to promote DNA replication and elicit cellular transformation was not due to a failure to interact with hsc70, since a nonfunctional chimera, containing the DnaJ J domain, bound hsc70. However, this nonfunctional chimeric T antigen was reduced in its ability to stimulate hsc70 ATPase activity and unable to liberate E2F from p130, indicating that transcriptional activation of factors required for cell growth and DNA replication may be compromised. Our data suggest that the T-antigen J domain harbors species-specific elements required for viral activities in vivo.

scholarly journals pRB-Dependent, J Domain-Independent Function of Simian Virus 40 Large T Antigen in Override of p53 Growth Suppression

2000 ◽  
Vol 74 (2) ◽  
pp. 864-874 ◽  
Author(s):  
Ole Gjoerup ◽  
Herta Chao ◽  
James A. DeCaprio ◽  
Thomas M. Roberts
Keyword(s):  
Transcriptional Repression ◽  
Simian Virus 40 ◽  
Cell Types ◽  
Simian Virus ◽  
Growth Suppression ◽  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
J Domain ◽  
Functional Inactivation

ABSTRACT Simian virus 40 (SV40) large T antigen (LT) can immortalize and transform many cell types. These activities are attributed in large part to the binding and functional inactivation by LT of two major tumor suppressors: p53 and the retinoblastoma protein, pRB. Most effects of LT on pRB have been shown to additionally require an intact J domain, which mediates binding to Hsc70. We show here that the J domain is not required for p53 override in full-length LT. Although LT binds p53, it was shown previously that overcoming a p53-induced cell cycle arrest requires binding to pRB family members (R. S. Quartin et al., J. Virol. 68:1334–1341). We demonstrate that an LT mutant defective for pRB family member binding (K1) can be complemented for efficient override of p53 arrest by a construct encoding the first 135 amino acids of LT with a J domain-inactivating mutation, H42Q. Hence, complementation does not require the J domain, and pRB binding by LT is important for more than dissociating pRB-E2F complexes, which is J dependent. In accordance with this notion, LT alleviates pRB small-pocket-mediated transcriptional repression independently of the J domain. The LT K1 mutant can also be complemented for p53 override by small t antigen (st) in a manner independent of its J domain. Our observations underscore the importance of multiple SV40 functions, two in LT and one in st, that act cooperatively to counteract p53 growth suppression.

scholarly journals Activation of the Tumor-Specific Death Effector Apoptin and Its Kinase by an N-Terminal Determinant of Simian Virus 40 Large T Antigen

2004 ◽  
Vol 78 (18) ◽  
pp. 9965-9976 ◽  
Author(s):  
Ying-Hui Zhang ◽  
Klaas Kooistra ◽  
Alexandra Pietersen ◽  
Jennifer L. Rohn ◽  
Mathieu H. M. Noteborn
Keyword(s):  
Nuclear Localization ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Chicken Anemia Virus ◽  
Nuclear Accumulation ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
Normal Cells ◽  
J Domain

ABSTRACT Apoptin, a viral death protein derived from chicken anemia virus, displays a number of tumor-specific behaviors. In particular, apoptin is phosphorylated, translocates to the nucleus, and induces apoptosis specifically in tumor or transformed cells, whereas it is nonphosphorylated and remains primarily inactive in the cytoplasm of nontransformed normal cells. Here, we show that in normal cells apoptin can also be activated by the transient transforming signals conferred by ectopically expressed simian virus 40 (SV40) large T antigen (LT), which rapidly induces apoptin's phosphorylation, nuclear accumulation, and the ability to induce apoptosis. Further analyses with mutants of LT showed that the minimum domain capable of inducing all three of apoptin's tumor-specific properties resided in the N-terminal J domain, a sequence which is largely shared by SV40 small t antigen (st). Interestingly, the J domain in st, which lacks its own nuclear localization signal (NLS), required nuclear localization to activate apoptin. These results reveal the existence of a cellular pathway shared by conditions of transient transformation and the stable cancerous or precancerous state, and they support a model whereby a transient transforming signal confers on apoptin both the upstream activity of phosphorylation and the downstream activity of nuclear accumulation and apoptosis induction. Such a pathway may reflect a general lesion contributing to human cancers.

Retroviral transduction of human periodontal cells with a temperature-sensitive SV40 large T antigen

1999 ◽  
Vol 44 (10) ◽  
pp. 823-834 ◽  
Author(s):  
M.H. Parkar ◽  
L. Kuru ◽  
M. O’Hare ◽  
H.N. Newman ◽  
F. Hughes ◽  
...  
Keyword(s):  
T Antigen ◽  
Temperature Sensitive ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
Retroviral Transduction

SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen

Cell ◽  
1987 ◽  
Vol 48 (2) ◽  
pp. 321-330 ◽  
Author(s):  
Ilan Bikel ◽  
Ximena Montano ◽  
Mounzer E. Agha ◽  
Myles Brown ◽  
Melissa McCormack ◽  
...  
Keyword(s):  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
Transformation Activity ◽  
Small T Antigen ◽  
Sv40 Small T

Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens

1986 ◽  
Vol 6 (4) ◽  
pp. 1204-1217
Author(s):  
P S Jat ◽  
C L Cepko ◽  
R C Mulligan ◽  
P A Sharp
Keyword(s):  
Cell Lines ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Vector System ◽  
Large T Antigen ◽  
T Antigens ◽  
Sv40 Large T Antigen ◽  
Polyomavirus Middle T Antigen ◽  
Middle T Antigen

We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV40) large T antigen and the polyomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat F111 cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorage-independent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.

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