Biomedical subjects

K V Visvanathan

Publications and source records attributed to K V Visvanathan.

5 recordsLinked to original sources

PubMed1992

Identification of novel factors that bind to the PRD I region of the human beta-interferon promoter.

Treatment of cells with virus or synthetic double-stranded RNA (dsRNA) leads to the transient transcriptional activation of the beta-interferon gene. Genetic analysis has revealed that the 5' regulatory sequence responsible for this induction contains multiple positive and negative elements. One of these, Positive Regulatory Domain I (PRD I), has been shown to bind the positively-acting transcription factor IRF-1. In this study we show that this element is inducible under conditions where IRF-1 cannot be detected, suggesting that additional cellular factors are involved in the induction process. To investigate the existence of such factors we have analysed the range and properties of PRD I-binding activities present in HeLa cells. In addition to the repressor protein IRF-2, several novel factors can bind to PRD I in uninduced cells: two of these have properties consistent with a role in negative regulation; levels of two others increase upon priming, and may be alternative candidates for activators. Upon induction we also observe a novel factor whose appearance does not depend upon de novo protein synthesis, and which appears to be a truncated form of IRF-2. The potential involvement of these factors in regulating the beta-interferon gene is discussed.

Base Sequence↗

PubMed1989

Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter.

The human beta-interferon promoter contains at least two positive acting domains (PRD I and PRD II). PRD I has been previously shown to stimulate basal transcription and to respond to induction by double-stranded RNA (dsRNA). Here we show that PRD II functions independently as a constitutive element that also responds to induction. A cellular factor that specifically binds to PRD II has been identified, and the levels of this factor increase markedly in extracts from cells treated with dsRNA. The inducible factor has a binding specificity that is indistinguishable from the transcription factor NF-kappa B. As has been shown for NF-kappa B, the PRD II-specific factor can be activated in uninduced extracts by treatment with detergent, suggesting that the inactive state is due to association with an inhibitory factor. Induction by dsRNA therefore provides a novel means for the post-translational activation of NF-kappa B. Potential binding sites for NF-kappa B are present in the 5' flanking regions of a number of genes involved in the immune response, several of which are inducible by dsRNA. These findings demonstrate a role for NF-kappa B in the physiological activation of genes in non-lymphoid cells.

Animals↗

PubMed1988

Preferential and novel activation of H-ras in human bladder carcinomas.

In a survey of primary human bladder carcinomas from 24 patients, using the NIH/3T3 transfection nude mouse tumor assay, we have detected an activated c-H-ras-1 gene in four cases. Two of these scored negative in primary transfections using a NIH/3T3 focus assay. Oligonucleotide analysis of genomic and enzymatically amplified DNA revealed substitution of valine at codon 12 in DNA from three transfectants and their parental carcinomas, which was absent from the DNA of normal tissue of each of these patients. The fourth activation was identified as a cysteine substitution at codon 13, a novel activation of c-H-ras-1 in a solid tumor sample. Thus, all seven activated ras genes reported in human urothelial tumors (Fujita et al., Proc. Natl. Acad. Sci. USA 82, 3849-3853, 1985) have been c-H-ras-1 genes, strongly suggesting that this member of the ras gene family is preferentially activated in cells of transitional origin.

Biological Assay↗

PubMed1985

Oncogenes and bladder cancer.

We screened a series of 15 superficial and invasive transitional cell carcinomas of the bladder for transforming activity on the NIH/3T3 transfection assay. In addition, by obtaining tumour DNA and normal lymphocyte DNA from the same patients we looked for evidence of gene amplification or rearrangement of the c-H-ras-1 gene by Southern blot analysis. One patient (with a grade 2T1 tumour) was shown to have an activated oncogene on the NIH/3T3 transfection assay and this was identified as a c-H-ras-1 gene. We could find no evidence of gene amplification or rearrangement of this gene in any tumour. The significance of activation of ras oncogenes in the pathogenesis of human bladder carcinoma is unclear.

Carcinoma, Transitional Cell↗

PubMedDate not supplied

Laboratory animals.

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Animal Experimentation↗