Functional role of BK virus tumor antigens in transformation

Nakshatri, Harikrishna; Pater, Mary M.; Pater, Alan

doi:10.1128/jvi.62.12.4613-4621.1988

Cited by 20 publications

(5 citation statements)

References 49 publications

(50 reference statements)

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“…6). The apparent molecular weights were affected little by the deletions, consistent with previous observations made while using the same monoclonal antibody and immunoprecipitation for BKV T-Ag deletion mutations (Simmons et al, 1977;Nakshatri et al, 1988). These reports proposed the explanation that the effects may be due to extensive posttranslational modifications.…”

Section: Region Of T-ag Required For Efficient Jcv 1 Transactivationsupporting

confidence: 87%

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Human JC Virus Nuclear Factor 1 Binding Motifs and Large Tumor Antigen Region Required for Transactivation of Late Promoter

Kumar

Devireddy

Tang

et al. 1996

Journal of Neurochemistry

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The nuclear factor 1 (NF‐1) motifs, NF‐1 II/III, in the two 98‐bp repeats of the transcription‐regulatory region of JC virus (JCV), have a critical role in brain‐specific transcription from the JCV early promoter‐enhancer. In this study, the role of these motifs in transactivation of the JCV late promoter‐enhancer (JCVL) was examined in differentiating glial P19 embryonal carcinoma cells. The expression of papovaviral large tumor antigen (T‐Ag) in the glial cells was shown by double immunofluorescence assays. By using site‐directed mutagenesis and in vivo assays, the two wild‐type NF‐1 II/III sites, but not the third site, were found to be essential for the transactivation of JCVL by JCV T‐Ag. In vitro transcription assays confirmed this specific transactivation and the transactivation was abolished by T‐Ag antibody. In electrophoretic mobility shift assays, expression of JCV T‐Ag increased the binding of a factor(s) to the 98‐bp repeat. T‐Ag antibody abolished the increase of binding. Binding assays with oligonucleotides of NF‐1 II/III motifs showed that the increased binding specifically required the wild‐type NF‐1 II/III sequences and confirmed the requirement of T‐Ag. To determine the region of T‐Ag necessary for transactivation of JCVL, the coding sequences were mutated. The amino‐terminal region of JCV Ag in amino acids 1–437 was essentially required for efficient transactivation. These results indicated that transactivation of JCVL and increased binding require a factor(s) found specifically in glial cells, the JCV NF‐1 II/III sites, and the T‐Ag amino‐terminal region.

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Section: Region Of T-ag Required For Efficient Jcv 1 Transactivationsupporting

confidence: 87%

“…1). The PAbIO8 monoclonal antibody, which recognizes SV4O T-Ag and reacts moderately well with JCV and BKV T-Ags (Nakshatri et al, 1988;BoIlag et al, 1989: Haggerty et al, 1989, was used. As a control, 0.5 pg HpaIdigested pRS V-/I-Gal was used.…”

Section: Runoff In Vitro Transcription Assaysmentioning

confidence: 99%

Human JC Virus Nuclear Factor 1 Binding Motifs and Large Tumor Antigen Region Required for Transactivation of Late Promoter

Kumar

Devireddy

Tang

et al. 1996

Journal of Neurochemistry

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“…We found this to be true in both our in vivo studies with monkey cell lysates and our in vitro studies with GST fusion proteins of the human retinoblastoma family members, suggesting that the interactions between BKV TAg and both monkey and human pRb family members are the same. Previous studies indicate that BKV TAg is normally expressed at low levels in a variety of host cells, including human embryonic kidney cells (5,62,66,74,76). In addition, BKV DNA levels in normal tissue surrounding urinary tract tumors are lower than in the tumors themselves (59).…”

mentioning

confidence: 99%

BK virus large T antigen: interactions with the retinoblastoma family of tumor suppressor proteins and effects on cellular growth control

Harris

Christensen

Imperiale

1996

J Virol

111

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BK virus (BKV) is a polyomavirus which infects a large percentage of the human population. It is a potent transforming agent and is tumorigenic in rodents. BKV DNA has also been found in human brain, pancreatic islet, and urinary tract tumors, implicating this virus in neoplastic processes. BKV T antigen (TAg) is highly homologous to simian virus 40 TAg, particularly in regions required for mitogenic stimulation and binding to tumor suppressor proteins. The experiments presented in this report show that BKV TAg can bind the tumor suppressor protein p53. BKV TAg also has the ability to bind to members of the retinoblastoma (pRb) family of tumor suppressor proteins both in vivo and in vitro. However, these interactions are detected only when large amounts of total protein are used, because the levels of BKV TAg normally produced from viral promoterenhancer elements are too low to bind a significant amount of the pRb family proteins in the cell. The low levels of BKV TAg produced by the viral promoter elements are sufficient to affect the levels and the phosphorylation patterns of these proteins and to induce serum-independent growth in these cells. Additional events, however, are required for full transformation. These data further support the notion that BKV TAg can affect cellular growth control mechanisms and may in fact be involved in neoplastic processes.

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“…The ATPase domain provides the energy needed for helicase activity. The outside surface of the helicase domain also binds to the tumour suppressor protein p53, thus preventing cell cycle arrest and apoptosis [ 37 , 38 , 39 , 41 ].…”

Section: The Bkpyv Proteinsmentioning

confidence: 99%

Biology of the BKPyV: An Update

Helle

Brochot

Handala

et al. 2017

Viruses

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The BK virus (BKPyV) is a member of the Polyomaviridae family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals may cause serious complications. In particular, with the implementation of more potent immunosuppressive drugs in the last decade, BKPyV has become an emerging pathogen in kidney and bone marrow transplant recipients where it often causes associated nephropathy and haemorrhagic cystitis, respectively. Unfortunately, no specific antiviral against BKPyV has been approved yet and the only therapeutic option is a modulation of the immunosuppressive drug regimen to improve immune control though it may increase the risk of rejection. A better understanding of the BKPyV life cycle is thus needed to develop efficient treatment against this virus. In this review, we provide an update on recent advances in understanding the biology of BKPyV.

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Functional role of BK virus tumor antigens in transformation

Cited by 20 publications

References 49 publications

Human JC Virus Nuclear Factor 1 Binding Motifs and Large Tumor Antigen Region Required for Transactivation of Late Promoter

Human JC Virus Nuclear Factor 1 Binding Motifs and Large Tumor Antigen Region Required for Transactivation of Late Promoter

BK virus large T antigen: interactions with the retinoblastoma family of tumor suppressor proteins and effects on cellular growth control

Biology of the BKPyV: An Update

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