The E2F5 repressor is an activator of E6/E7 transcription and of the S-phase entry in HPV18-associated cells

Teissier, Sébastien; Pang, Chai Ling; Thierry, Françoise

doi:10.1038/onc.2010.246

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…Recently, it has been shown that E2F5 positively regulates S‐phase entry in HeLa cells and that this activation of the cell cycle is specific for HPV18‐expressing cells. This suggested that HPV18 could act changing the role of E2F5 from being a cell‐cycle repressor to an activator, thus contributing to the higher oncogenic potential of HPV18 respect to other high‐risk HPV types (Teissier et al, 2010).…”

Section: Prb and E2f Family In Cancermentioning

confidence: 99%

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

Fiore

D’Anneo

Tesoriere

et al. 2013

Journal Cellular Physiology

168

127

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Loss of RB1 gene is considered either a causal or an accelerating event in retinoblastoma. A variety of mechanisms inactivates RB1 gene, including intragenic mutations, loss of expression by methylation and chromosomal deletions, with effects which are species-and cell typespecific. RB1 deletion can even lead to aneuploidy thus greatly increasing cancer risk. The RB1gene is part of a larger gene family that includes RBL1 and RBL2, each of the three encoding structurally related proteins indicated as pRb, p107, and p130, respectively. The great interest in these genes and proteins springs from their ability to slow down neoplastic growth. pRb can associate with various proteins by which it can regulate a great number of cellular activities. In particular, its association with the E2F transcription factor family allows the control of the main pRb functions, while the loss of these interactions greatly enhances cancer development. As RB1 gene, also pRb can be functionally inactivated through disparate mechanisms which are often tissue specific and dependent on the scenario of the involved tumor suppressors and oncogenes. The critical role of the context is complicated by the different functions played by the RB proteins and the E2F family members. In this review, we want to emphasize the importance of the mechanisms of RB1/pRb inactivation in inducing cancer cell development. The review is divided in three chapters describing in succession the mechanisms of RB1 inactivation in cancer cells, the alterations of pRb pathway in tumorigenesis and the RB protein and E2F family in cancer.

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Section: Prb and E2f Family In Cancermentioning

confidence: 99%

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

Fiore

D’Anneo

Tesoriere

et al. 2013

Journal Cellular Physiology

168

127

View full text Add to dashboard Cite

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“…The impact of the S-phase environment on the viral life cycle is not restricted to lytic viral replication but is also involved in the episomal genome maintenance during viral latency or reactivation processes, as was recently shown for EBV and the Kaposi’s Sarcoma-associated herpesvirus (KSHV) [34], [35]. Strikingly, infections with oncogenic viruses (e.g., SV40, HPV, HTLV-1, EBV) are often associated with S-phase deregulation and genomic instability, preferentially occurring during this critical phase of the cell cycle [24], [27], [33], [36].…”

Section: Introductionmentioning

confidence: 99%

Cell Cycle Modulation by Marek’s Disease Virus: The Tegument Protein VP22 Triggers S-Phase Arrest and DNA Damage in Proliferating Cells

et al. 2014

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Marek’s disease is one of the most common viral diseases of poultry affecting chicken flocks worldwide. The disease is caused by an alphaherpesvirus, the Marek’s disease virus (MDV), and is characterized by the rapid onset of multifocal aggressive T-cell lymphoma in the chicken host. Although several viral oncogenes have been identified, the detailed mechanisms underlying MDV-induced lymphomagenesis are still poorly understood. Many viruses modulate cell cycle progression to enhance their replication and persistence in the host cell, in the case of some oncogenic viruses ultimately leading to cellular transformation and oncogenesis. In the present study, we found that MDV, like other viruses, is able to subvert the cell cycle progression by triggering the proliferation of low proliferating chicken cells and a subsequent delay of the cell cycle progression into S-phase. We further identified the tegument protein VP22 (pUL49) as a major MDV-encoded cell cycle regulator, as its vector-driven overexpression in cells lead to a dramatic cell cycle arrest in S-phase. This striking functional feature of VP22 appears to depend on its ability to associate with histones in the nucleus. Finally, we established that VP22 expression triggers the induction of massive and severe DNA damages in cells, which might cause the observed intra S-phase arrest. Taken together, our results provide the first evidence for a hitherto unknown function of the VP22 tegument protein in herpesviral reprogramming of the cell cycle of the host cell and its potential implication in the generation of DNA damages.

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“…The E6 and E7 oncoproteins have been shown to be key mediators of the development of HPV-induced cervical carcinoma. HPV-related transcription factors are involved in the G1/S and G2/M transition within the cell cycle (9). The E6 protein, which associates with E6-associated protein (E6AP), induces p53 degradation…”

Section: Introductionmentioning

confidence: 99%

Luteolin induces intrinsic apoptosis via inhibition of E6/E7 oncogenes and activation of extrinsic and intrinsic signaling pathways in HPV-18-associated cells

et al. 2014

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Luteolin, a flavonoid extracted from a number of plants with recognized anticancer, anti-inflammatory and anti-oxidative activities, inhibits angiogenic processes and modulates multidrug resistance. However, the efficacy and mechanisms of action of this flavonoid agent are still undergoing study. In order to elucidate whether luteolin exhibits an anticancer effect in cervical cancer cells, HeLa cells were incubated with luteolin and apoptosis was assessed by observing nuclear morphological changes, and performing Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Cell cycle analysis, western blotting, RT-PCR and mitochondrial membrane potential measurements were also carried out. Luteolin showed a significant dose-dependent cytotoxic effect only in human papillomavirus (HPV)-positive cervical cancer cells, when compared to its effect on HPV-negative cervical cancer C33A cells. Expression levels of human papilloma virus E6 and E7 oncogenes were suppressed, those of related factors pRb and p53 were recovered and E2F5 was increased by luteolin treatment. Furthermore, luteolin enhanced the expression of death receptors and death receptor downstream factors such as Fas/FasL, DR5/TRAIL and FADD in HeLa cells, and activated caspase cascades. In particular, luteolin enhanced the activity of caspase-3 and -8 in a dose-dependent manner. Activation of caspase-3 induced caspase-8 activity and vice versa. Luteolin also induced mitochondrial membrane potential collapse and cytochrome c release, and inhibited Bcl-2 and Bcl-xL expression. In conclusion, luteolin exerts anticarcinogenic activity through inhibition of E6 and E7 expression and cross-activation of caspase-3 and -8. Taken together, these results suggest that luteolin induces inactivation of HPV-18 oncogene expression and apoptosis by activating the intrinsic and extrinsic pathways.

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The E2F5 repressor is an activator of E6/E7 transcription and of the S-phase entry in HPV18-associated cells

Cited by 17 publications

References 29 publications

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

Cell Cycle Modulation by Marek’s Disease Virus: The Tegument Protein VP22 Triggers S-Phase Arrest and DNA Damage in Proliferating Cells

Luteolin induces intrinsic apoptosis via inhibition of E6/E7 oncogenes and activation of extrinsic and intrinsic signaling pathways in HPV-18-associated cells

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