Identification of sequences responsible for positive and negative regulation by E1A in the promoter of H-2Kbm1 class I MHC gene.

Katoh, Shigeki; Ozawa, Kazuo; Kondoh, Satoshi; Soeda, E.; Israël, Alain; Shiroki, Kazuko; Fujinaga, Kei; Itakura, Keiichi; Gachelin, Gabriel; Yokoyama, Kazunari K.

doi:10.1002/j.1460-2075.1990.tb08088.x

Cited by 53 publications

(34 citation statements)

References 44 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have also found that constitutive ICS-binding activity is very low in the CNS (56). Additional regulatory elements present upstream from region I and downstream from the ICS have been reported (13,33,38,71). These studies have provided a foundation on which to further investigate the regulatory mechanisms of MHC class I gene expression.…”

supporting

confidence: 59%

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

et al. 1992

View full text Add to dashboard Cite

The major histocompatibility complex (MHC) class I HLA-B7 transgene carrying a 660-bp upstream sequence is expressed in the mouse with tissue specificity that parallels that of the expression of endogenous mouse MHC class I (H-2) genes. We have performed in vivo genomic footprinting for the HLA-B7 transgene and the endogenous HN2Kb gene. We show that the upstream region of both the transgene and the endogenous gene was extensively occupied in spleen tissue, where these genes are expressed at high levels. In contrast, no occupancy was detected in brain tissue, where expression of these genes is virtually absent. Sites exhibiting in vivo protection correspond to cis elements previously shown to bind to nuclear factors in vitro, including the constitutive enhancer region I and the interferon response element. The strongest tissue-specific protection was detected at site a, located downstream from the interferon response element. Site of bound a constitutively expressed nuclear factor(s) in vitro that exhibited an overlapping specificity which may involve a nuclear hormone receptor, RXR, and an AP-1-related factor. Site a was functional in vivo, as it enhanced MHC class I transcription in lymphocytes. These results show that the tissue-specific occupancy of the MHC class I regulatory sequences in vivo correlates with their expression and suggest that in vivo occupancy is controlled by a mechanism other than the mere presence of factors capable of binding to these sites. Our results suggest that a sequence present in the 660-bp upstream region in a human leukocyte antigen gene directs tissue-specific occupancy of MHC class I genes in vivo, independently of their position and copy number, illustrating a potential advantage of using a transgene for delimitation of the sequence requirement for in vivo occupancy.

show abstract

supporting

confidence: 59%

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

et al. 1992

View full text Add to dashboard Cite

show abstract

“…on the activity of CEA promoter in plasmid co-transfection experiments. Plasmid pGL3-CEApr, which carries the gene for firefly luciferase directed by the CEA promoter was provided by the RIKEN DNA Bank (Tsukuba, Ibaraki, Japan) and plasmid pE1A5.13S, 41 which carries the E1A-13S gene of Ad type 5, was provided by Dr Shiroki (Tokyo University, Tokyo, Japan). Plasmid pSV-b-galactosidase, which carries a gene for b-galactosidase directed by the senminum virus 40 promoter; plasmid phRL-TK, which carries the gene for Renilla luciferase; and plasmid pGL3-basic, which carries the gene for firefly luciferase were purchased from Promega (Madison, WI).…”

Section: Viral Vectorsmentioning

confidence: 99%

E1A, E1B double-restricted replicative adenovirus at low dose greatly augments tumor-specific suicide gene therapy for gallbladder cancer

et al. 2008

View full text Add to dashboard Cite

Combination therapy with replicative oncolytic viruses is a recent topic in innovative cancer therapy, but few studies have examined the efficacy of oncolytic adenovirus plus replication-deficient adenovirus carrying a suicide gene. We aim to evaluate whether an E1A, E1B double-restricted oncolytic adenovirus, AxdAdB-3, can improve the efficacy for gallbladder cancers (GBCs) of the replication-deficient adenovirus-based herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) therapy directed by the carcinoembryonic antigen (CEA) promoter. Cytopathic effects of AxdAdB-3 plus AxCEAprTK (an adenovirus expressing HSVtk directed by CEA promoter) or AxCAHSVtk (an adenovirus expressing HSVtk directed by a nonspecific CAG promoter) with GCV administration were examined in several GBC lines and normal cells. Efficacy in vivo was tested in severe combined immunodeficiency disease mice with GBC xenografts. Addition of AxdAdB-3 (1 multiplicity of infection, MOI) significantly enhanced the cytopathic effects of AxCEAprTK (10 MOI)/GCV on GBC cells. The augmented effect was attributable to the replication of the AxCEAprTK and also to the enhanced CEA promoter activity, which was presumably transactivated by E1A. In normal cells, AxdAdB-3 (20 MOI) plus AxCEAprTK (200 MOI)/GCV was not cytopathic, whereas AxdAdB-3 (1 MOI) plus AxCAHSVtk (10 MOI)/GCV was significantly toxic. Low-dose AxdAdB-3 (2 Â 10 7 PFU, plaque-forming unit) plus AxCEAprTK (2 Â 10 8 PFU)/GCV significantly suppressed the growth of GBC xenografts as compared with either AxdAdB-3 (2 Â 10 7 PFU)/GCV or AxCEAprTK (2 Â 10 9 PFU)/GCV alone. E1A, E1B double-restricted replicating adenovirus at low dose significantly augmented the efficacy of CEA promoter-directed HSVtk/GCV therapy without obvious toxicity to normal cells, suggesting a potential use of this combination for treating GBC and other CEA-producing malignancies.

show abstract

“…and is a function of E1A. A limited number of cellular genes undergo negative regulation by E1A, including genes encoding two surface receptors, neu and HER2 (62), major histocompatibility complex class I (MHC-I) genes (31), and some differentiation genes (4). MHC-I downregulation is mediated only by the Ad12 E1A (a member of adenovirus subgroup A) and not Ad5 E1A (subgroup C).…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β1 Receptor II Is Downregulated by E1A in Adenovirus-Infected Cells

Tarakanova

Wold

2003

J Virol

View full text Add to dashboard Cite

Transforming growth factor ␤1 (TGF-␤1) signaling is compromised in many tumors, thereby allowing the tumor to escape the growth-inhibitory and proapoptotic activities of the cytokine. Human adenoviruses interfere with a number of cellular pathways involved in cell cycle regulation and apoptosis, initially placing the cell in a "tumor-like" state by forcing quiescent cells into the cell cycle and also inhibiting apoptosis. We report that adenovirus-infected cells resemble tumor cells in that TGF-␤1 signaling is inhibited. The levels of TGF-␤1 receptor II (T␤RII) in adenovirus-infected cells were decreased, and this decrease was mapped, by using virus mutants, to the E1A gene and to amino acids 2 to 36 and the C-terminal binding protein binding site in the E1A protein. The decrease in the T␤RII protein was accompanied by a decrease in T␤RII mRNA. The decrease in T␤RII protein levels in adenovirus-infected cells was greater than the decrease in T␤RII mRNA, suggesting that downregulation of the T␤RII protein may occur through more than one mechanism. Surprisingly in this context, the half-lives of the T␤RII protein in infected and uninfected cells were similar. TGF-␤1 signaling was compromised in cells infected with wild-type adenovirus, as measured with 3TP-lux, a TGF-␤-sensitive reporter plasmid expressing luciferase. Adenovirus mutants deficient in T␤RII downregulation did not inhibit TGF-␤1 signaling. TGF-␤1 pretreatment reduced the relative abundance of adenovirus structural proteins in infected cells, an effect that was potentiated when cells were infected with mutants incapable of modulating the TGF-␤ signaling pathway. These results raise the possibility that inhibition of TGF-␤ signaling by E1A is a means by which adenovirus counters the antiviral defenses of the host.

show abstract

Identification of sequences responsible for positive and negative regulation by E1A in the promoter of H-2Kbm1 class I MHC gene.

Cited by 53 publications

References 44 publications

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

E1A, E1B double-restricted replicative adenovirus at low dose greatly augments tumor-specific suicide gene therapy for gallbladder cancer

Transforming Growth Factor β1 Receptor II Is Downregulated by E1A in Adenovirus-Infected Cells

Contact Info

Product

Resources

About