Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus

Caracciolo, Valentina; Reiss, Krzysztof; Khalili, Kamel; Falco, Giulia De; Giordano, Antonio

doi:10.1038/sj.onc.1209681

Cited by 52 publications

(48 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16). More than 80% of neonatal hamsters inoculated intracerebrally, i.p., or s.c. with strains of JCV, isolated from progressive multifocal leukoencephalopathy lesions, develop a wide range of tumors including medulloblastomas, neuroblastomas, and pineocytomas (16,17). Although the mechanism of JCV-induced neurotumorigenesis is not entirely clear, several studies point to the involvement of the viral early protein, T antigen, in this process.…”

Section: Molecular Biology Of Medulloblastomamentioning

confidence: 99%

Medulloblastoma: From Molecular Pathology to Therapy

Rossi

Caracciolo²,

Russo

et al. 2008

Clinical Cancer Research

156

134

View full text Add to dashboard Cite

Medulloblastoma is the most common malignant tumor of central nervous system in children.Patients affected by medulloblastoma may be categorized as high-risk and standard-risk patients, based on the clinical criteria and histologic features of the disease. Currently, multimodality treatment, including surgery, radiotherapy, and chemotherapy is considered as the most effective strategy against these malignant cerebellar tumors of the childhood. Despite the potential poor outcomes of these lesions, the 5-year survival stands, at present, at 70% to 80% for standard-risk patients, whereas high-risk patients have a 5-year survival of 55% to 76%. Attempts to further reduce the morbidity and mortality associated with medulloblastoma have been restricted by the toxicity of conventional treatments and the infiltrative nature of the disease. Over the past decade, new discoveries in molecular biology have revealed new insights in signaling pathways regulating medulloblastoma tumor formation. Recent advances in the molecular biology of medulloblastoma indicate that the classification of these embryonal tumors, solely based on histology and clinical criteria, may not be adequate enough. Better understanding of the growth control mechanisms involved in the development and progression of medulloblastoma will allow a better classification, leading to the improvement of the existing therapies, as well as to the development of new therapeutic approaches.

show abstract

Section: Molecular Biology Of Medulloblastomamentioning

confidence: 99%

Medulloblastoma: From Molecular Pathology to Therapy

Rossi

Caracciolo²,

Russo

et al. 2008

Clinical Cancer Research

156

134

View full text Add to dashboard Cite

show abstract

“…When we used siRNAs to downregulate ICBP90 and DNMT1 expressions, we observed that pRB expression was increased in Jurkat cells and HVTs-SM1. Nevertheless, since HVTs-SM1 have inactivated pRB, due to the interaction with large T antigen (Caracciolo et al, 2006;Giacinti and Giordano, 2006), a direct involvement of pRB in the mechanism of action of ICBP90 on VEGF gene expression seems unlikely. Interestingly, downregulation of ICBP90 (present results) and DNMT1 (Fournel et al, 1999 and present is a negative regulator of the VEGF gene expression (Miki et al, 2001), we propose that the ICBP90/DNMT1 complex can control VEGF expression via a downregulation of the p16 INK4A gene.…”

Section: Icbp90 Interacts With Dnmt1 and Regulates Vegf Expression M mentioning

confidence: 99%

The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression

et al. 2007

Self Cite

View full text Add to dashboard Cite

Inverted CCAAT box-binding protein of 90 kDa (ICBP90) is over-expressed in several types of cancer, including breast, prostate and lung cancers. In search for proteins that interact with the set and ring-associated (SRA) domain of ICBP90, we used the two-hybrid system and screened a placental cDNA library. Several clones coding for a new domain of DNMT1 were found. The interaction, between the ICBP90 SRA domain and the DNMT1 domain, has been confirmed with purified proteins by glutathione-Stransferase pull-down experiments. We checked whether ICBP90 and DNMT1 are present in the same macromolecular complexes in Jurkat cells and immortalized human vascular smooth muscle cells (HVTs-SM1). Coimmunoprecipitation experiments showed that ICBP90 and DNMT1 are present in the same molecular complex, which was further confirmed by co-localization experiments as assessed by immunocytochemistry. Downregulation of ICBP90 and DNMT1 decreased VEGF gene expression, a major pro-angiogenic factor, whereas those of p16 INK4A gene and RB1 gene were significantly enhanced. Together, these results indicate that DNMT1 and ICBP90 are involved in VEGF gene expression, possibly via an interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 and an upregulation of p16 INK4A. They further suggest a new role of ICBP90 in the relationship between histone ubiquitination and DNA methylation in the context of tumoral angiogenesis and tumour suppressor genes silencing.

show abstract

“…T-Ag can induce aberrant cell cycle entry and S-phase initiation in a variety of somatic phenotypes, through its binding to the tumor suppressor retinoblastoma protein (Rb) and consequent derepression of Rb targets (16,(32)(33)(34)(35). Whereas some mitotic phenotypes may undergo neoplastic transformation by this process (and the polyomaviruses have been causally linked to oncogenesis in various species and cell types; refs.…”

Section: Jcv Efficiently Infects Astroglia and Their Progenitors In Cmentioning

confidence: 99%