Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methyl chloride (MeCl) is an abundant environmental mutagen and carcinogen and may be one of several environmental alkylating agents against which the protection of an adaptive response is required in microorganisms. Both MeCl and methyl iodide (MeI), at micromolar concentrations, induced the adaptive response to alkylation damage in Escherichia coli. This response is regulated by the Ada protein which is converted into a transcriptional activator by self-methylation on repair of methylphosphotriesters in methylated DNA. However, using high amounts of Ada protein, activation of Ada occurred in vitro following direct protein methylation by both MeI (in agreement with previously published data) and MeCl. Activation was enhanced when methyl halide treatments were performed in the presence of DNA. An unadapted E. coli cell contains only 2 to 4 molecules of Ada protein, and presents an extremely small target of 2 to 4 specific cysteine residues per cell for activation of Ada by direct protein methylation in vivo. Thus, it is proposed that induction of the adaptive response in vivo initially occurs via efficient repair by the Ada protein of a low number of methylphosphotriesters in DNA. When the cellular Ada protein level has substantially increased, a greater probability of direct methylation and activation of Ada at cysteine-69 by MeCl may sustain and further increase induction of the adaptive response.
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PMID:Induction of the adaptive response of Escherichia coli to alkylation damage by the environmental mutagen, methyl chloride. 767 75

A novel system that leaks beta-galactosidase (beta-gal) without a requirement for secretion or export signals was developed in Lactococcus lactis by controlled expression of integrated phage holin and lysin cassettes. The late promoter of the lytic lactococcal bacteriophage phi31 is an 888-bp fragment (P(15A10)) encoding the transcriptional activator. When a high-copy-number P(15A10)::lacZ.st fusion was introduced into L. lactis strains C10, ML8, NCK203, and R1/r1t, high levels of the resultant beta-gal activity were detected in the supernatant (approximately 85% of the total beta-gal activity for C10, ML8, and NCK203 and 45% for R1/r1t). Studies showed that the phenotype resulted from expression of Tac31A from the P(15A10) fragment, which activated a homologous late promoter in prophages harbored by the lactococcal strains. Despite the high levels of beta-gal obtained in the supernatant, the growth of the strains was not significantly affected, nor was there any evidence of severe membrane damage as determined by using propidium iodide or transmission electron microscopy. Integration of the holin-lysin cassette of phage r1t, under the control of the phage phi31 late promoter, into the host genome of MG1363 yielded a similar "leaky" phenotype, indicating that holin and lysin might play a critical role in the release of beta-gal into the medium. In addition to beta-gal, tetanus toxin fragment C was successfully delivered into the growth medium by this system. Interestingly, the X-prolyl dipeptidyl aminopeptidase PepXP (a dimer with a molecular mass of 176 kDa) was not delivered at significant levels outside the cell. These findings point toward the development of bacterial strains able to efficiently release relevant proteins and enzymes outside the cell in the absence of known secretion and export signals.
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PMID:Leaky Lactococcus cultures that externalize enzymes and antigens independently of culture lysis and secretion and export pathways. 1113 53

Retinoblastoma (RB), a malignant tumour of the eye arising from developing retina, is the most frequent primary intraocular malignancy of childhood. Its primary management with chemotherapy involves combination regimen of etoposide, vincristine and carboplatin and intra vitreal chemotherapy using melphalan when vitreous seeds develop. Radiotherapy is another effective mode in treating RB. We recently explored the notion if radiotherapy in RB can be mediated via Sodium Iodide Symporter (NIS), an intrinsic membrane glycoprotein which is a key regulator of iodide access to thyroid gland. Its expression has been exploited successfully for diagnostic imaging and molecular radionuclide-based therapy of thyroid cancer. We determined that NIS is expressed endogenously in RB tumour tissues, and in retinoblastoma cell lines Y79 and Weri-Rb-1, and therefore made an attempt to enhance the endogenously low expression of NIS protein in both Y79 and Weri-Rb-1 cells. Here we report about the potential of bovine lactoferrin (bLf) which is a known chemo preventive and emerging safe anti-cancer bio drug, as well as a natural transcriptional activator of genes, to enhance the endogenous expression of NIS in Y79 and Weri-Rb-1 cells. Real time PCR revealed that both cell lines express mRNA of lactoferrin receptors while flow cytometry and confocal microscopy showed the cells efficiently internalize bLf which upregulates NIS expression. These findings highlight an important step that could be taken towards the development of less harmful approaches for the treatment of RB by employing natural supplement bLf (with its clinically proven safe profile), and warrants further studies in future, focussing on enhancing NIS expression in RB cells and NIS functional assays in these cells.
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PMID:Upregulation of sodium iodide symporter (NIS) protein expression by an innate immunity component: Promising potential for targeting radiosensitive retinoblastoma. 3279 40