Epstein-Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells.
Ming-Tsan Liu,Yi-Ren Chen,Shu-Chuan Chen,Chi-Yuan Hu,Chang-Shen Lin,Yu-Ting Chang,Won-Bo Wang,Jen-Yang Chen,Jen-Yang Chen +8 more
TLDR
It is suggested that disruption of DNA repair by LMP-1 results in an accumulation of unrepaired DNA and consequent genomic instability, which may contribute to the oncogenesis of LMP1 in human epithelial cells.Abstract:
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a viral oncogene and it is essential for the transformation of resting B cells by the virus. The protein acts as a ligand-less membrane receptor and triggers numerous cellular signaling pathways. Cellular transformation frequently has been associated with genomic instability. To investigate whether EBV LMP1 induces chromosomal aberrations, micronucleus (MN) formation was examined in LMP1-expressing epithelial cells. The expression of wild-type LMP1 enhanced both spontaneous and bleomycin-induced MN formation. MN formation may be induced by inactivation of DNA repair and, therefore, we investigated the effect of LMP1 on DNA repair, using a host cell reactivation (HCR) assay. In the HCR assay, LMP1 reduced the capacity for DNA repair of both NPC-TW01 (p53-wild-type) and H1299 (p53-deficient) cells. As reduction of DNA repair by LMP1 occurs in p53-wild-type and p53-deficient cells, it seems that LMP1 can repress DNA repair in a p53-independent manner. Inactivation of DNA repair may render cells sensitive to DNA-damaging agents. In this study, H1299 cells harboring LMP1 were shown to be more sensitive to UV and bleomycin than those with a vector control. Using various deletion mutants of EBV LMP1 to determine the regions of LMP1 required to enhance MN formation, inhibit DNA repair and sensitize cells to DNA-damaging agents, we found that the region a. a. 189-222 (located within the CTAR1 domain) was responsible for sensitizing cells to UV and bleomycin, as well as for enhancing MN formation and repressing DNA repair. Based on these results, we suggest that disruption of DNA repair by LMP-1 results in an accumulation of unrepaired DNA and consequent genomic instability, which may contribute to the oncogenesis of LMP1 in human epithelial cells.read more
Citations
More filters
Journal ArticleDOI
The Metabolic Basis Of Inherited Disease.
TL;DR: This volume, more than most, explains the contributions of the laboratory to clinical medicine, and shedding light on fundamental metabolic sequences and biologic mechanisms.
iArc monogrAphs on the evAluAtion oF cArcinogenic risks to humAns
TL;DR: PReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl
Journal ArticleDOI
Modulation of LMP1 protein expression by EBV-encoded microRNAs
Angela K. F. Lo,Ka Fai To,Kwok Wai Lo,Raymond W.M. Lung,Jan Wai Ying Hui,Gangling Liao,S. Diane Hayward +6 more
TL;DR: Insight is provided into the discrepancy between LMP1 transcript and protein detection in NPC and the role of the EBV miRNAs in regulating L MP1 downstream signaling to promote cancer development is highlighted.
Journal ArticleDOI
The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species
Bettina Gruhne,Ramakrishna Sompallae,Diego Marescotti,Siamak A. Kamranvar,Stefano Gastaldello,Maria G. Masucci +5 more
TL;DR: It is shown that EBNA-1 induces chromosomal aberrations, DNA double-strand breaks, and engagement of the DNA damage response (DDR), and these signs of genomic instability are associated with the production of reactive oxygen species (ROS) and are reversed by antioxidants.
Journal ArticleDOI
Three Epstein-Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints
TL;DR: Multiple cellular functions involved in the maintenance of genome integrity seem to be independently targeted by EBV, pointing to the induction of genomic instability as a critical event in viral oncogenesis.
References
More filters
Book
The metabolic basis of inherited disease
TL;DR: The metabolic basis of inherited disease, the metabolic basis for inherited disease as mentioned in this paper, The metabolic basis in inherited disease and inherited diseases, and inherited disease diagnosis and management, in the context of inherited diseases
Journal ArticleDOI
Adult T-cell leukemia : antigen in an ATL cell line and detection of antibodies to the antigen in human sera
Yorio Hinuma,Kinya Nagata,Masao Hanaoka,Masuyo Nakai,Tadashi Matsumoto,Ken-Ichiro Kinoshita,Shigeru Shirakawa,Isao Miyoshi +7 more
TL;DR: Antibodies against the antigen in MT-1 cells were found in all 44 patients with ATL examined and in 32 of 40 patients with malignant T-cell lymphomas (most of them had diseases similar to ATL except that leukemic cells were not found in the peripheral blood).
Journal ArticleDOI
The causes and prevention of cancer.
TL;DR: Epidemiological evidence indicates that avoidance of smoking, increased consumption of fruits and vegetables, and control of infections will have a major effect on reducing rates of cancer.
Journal ArticleDOI
Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis.
TL;DR: It is indicated that EBV is related to, and probably the cause of, infectious mononucleosis, and that the agent has a world-wide dissemination.