Simian virus 40 large T overcomes p300 repression of c-Myc

Microbiology and Immunology Department, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Virology (Impact Factor: 3.32). 09/2008; 377(2):227-32. DOI: 10.1016/j.virol.2008.04.042
Source: PubMed


We previously showed that in quiescent cells p300/CBP negatively regulates the cell cycle G1-S transition by keeping c-Myc in a repressed state and that adenovirus E1A induces c-Myc by binding to p300/CBP. Studies have shown that p300/CBP binding to simian virus 40 large T is indirect and mediated by p53. By using a series of large T mutants that fail to bind to various cellular proteins including p53 as well as cells where p300 is overexpressed or p53 is knocked down, we show that the association of large T with p300 contributes to the induction of c-Myc and the cell cycle. The induction of c-Myc by this mechanism is likely to be important in large T mediated cell cycle induction and cell transformation.

Download full-text


Available from: Ravi Kumar Kadeppagari, Sep 08, 2015
  • Source
    • "Moreover, a stabilized c-Myc mutant can substitute for t-antigen expression in cell culture transformation assays (Sablina and Hahn 2008), again suggesting that endogenous Myc is a bona fide downstream effector of small t. Large T's association with p300 is also thought to promote c-Myc activity and potentiate large T-mediated cell cycle entry and cell transformation (Singhal et al. 2008). Of note, the b cells within the regressed islet tumors in Omomyc-expressing TRE-Omomyc; CMVrtTA;RIP1-Tag2 mice remain clearly transformed even when Myc is inhibited. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The ubiquitous deregulation of Myc in human cancers makes it an intriguing therapeutic target, a notion supported by recent studies in Ras-driven lung tumors showing that inhibiting endogenous Myc triggers ubiquitous tumor regression. However, neither the therapeutic mechanism nor the applicability of Myc inhibition to other tumor types driven by other oncogenic mechanisms is established. Here, we show that inhibition of endogenous Myc also triggers ubiquitous regression of tumors in a simian virus 40 (SV40)-driven pancreatic islet tumor model. Such regression is presaged by collapse of the tumor microenvironment and involution of tumor vasculature. Hence, in addition to its diverse intracellular roles, endogenous Myc serves an essential and nonredundant role in coupling diverse intracellular oncogenic pathways to the tumor microenvironment, further bolstering its credentials as a pharmacological target.
    Genes & development 05/2011; 25(9):907-16. DOI:10.1101/gad.2038411 · 10.80 Impact Factor
  • Source
    • "Although LT binds p300/CBP using p53 as an adaptor, recent work based on " patch " surface mutants of LT indicates that LT also directly makes contact with p300/CBP, and this is required for oncogenic transformation (Ahuja et al., 2009). The critical targets modulated by LT binding to p300/ CBP largely remain to be identified, but one of them appears to be induction of c-myc (Singhal et al., 2008). As with p300, p400 was first identified as a component of E1A immunocomplexes (Barbeau et al., 1994). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over 50 years of polyomavirus research has produced a wealth of insights into not only general biologic processes in mammalian cells, but also, how conditions can be altered and signaling systems tweaked to produce transformation phenotypes. In the past few years three new members (KIV, WUV, and MCV) have joined two previously known (JCV and BKV) human polyomaviruses. In this review, we present updated information on general virologic features of these polyomaviruses in their natural host, concentrating on the association of MCV with human Merkel cell carcinoma. We further present a discussion on advances made in SV40 as the prototypic model, which has and will continue to inform our understanding about viruses and cancer.
    Advances in Cancer Research 01/2010; 106:1-51. DOI:10.1016/S0065-230X(10)06001-X · 5.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Two ball lens systems are frequently used for single mode fiber-to-fiber coupling. Sapphire is often considered for this type of application due to its high index (for reduced spherical aberration) and its mechanical integrity. However, sapphire is negative uniaxial, and the effect of optical birefringence on coupling loss has not been formally studied for ball lenses. Therefore, the purpose of this study is to determine if Poynting vector walk-off of the e-wave, which leads to beam displacement, contributes adversely to coupling loss (birefringence aberration)
    Journal of Lightwave Technology 01/1995; 14(3). DOI:10.1109/LEOS.1995.484767 · 2.97 Impact Factor
Show more