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)

The p56lck tyrosine kinase is most likely to be involved in signal transduction of T lymphocyte activation. After full activation through the TcR/CD3 complex lck mRNA is transiently down-modulated. This down-modulation was due to an early decrease of both transcription and stability of the lck mRNA. To study the involvement of transcriptional and post-transcriptional factors in this regulations, we have analysed the effect of cycloheximide, a protein synthesis inhibitor, on the steady-state of the lck mRNA. Cycloheximide superinduced lck mRNA by increasing its stability, although cycloheximide concomitantly decreased lck transcription. This suggests that the constitutive level of lck mRNA observed prior to activation is controlled by transcriptional activator(s) and post-transcriptional destabilizing factor(s). Second, lck mRNA down-modulation observed after full activation was inhibited by cycloheximide. It increased lck mRNA stability whereas lck transcription remained low. Therefore, full activation might increase the synthesis and/or activity of destabilizing factor(s). Cyclosporin A also inhibited the down-modulation of lck mRNA by increasing its transcription with no effect on its stability. Since, lck mRNA down-modulation was always associated with lymphokine mRNA induction, and since CsA blocks both lymphokine transcription and lck decrease of transcription, this indicates that these genes might share common regulatory pathways leading to their inverse transcriptional regulation.
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PMID:Down-regulation of lck mRNA by T cell activation involves transcriptional and post-transcriptional mechanisms. 183 93

Interleukin 1 (IL 1) is a protein produced by monocytes in response to certain antigens which produces a wide variety of cellular responses in various tissues. We have studied the regulation of the human proIL-1 beta gene in THP-1 human monocytic leukemia cells. Lipopolysaccharide (LPS) induction of this gene results in an immediate and transient increase of message that rapidly falls to a low, but constant, level within 6 hr. This decrease results from a specific repression of transcription by 2 hr after stimulation. Cycloheximide inhibition of new protein synthesis causes a superinduction of IL 1 message, but does not alter the initial kinetics of message production. This presumably delays the synthesis of a labile transcriptional repressor protein and implies that the proIL-1 beta gene is under the control of both a transcriptional activator and a newly synthesized transcriptional repressor. The transient increase in mRNA production and the sustained low-level synthesis beyond the initial transient response suggest that the IL 1 protein itself may act intracellularly in a manner analogous to that described for several proto-oncogenes and cellular competence factors.
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PMID:Transcriptional regulation of the human prointerleukin 1 beta gene. 349 77

In WI-38 human fibroblasts, interleukin-1 beta and tumour necrosis factor-alpha (TNF-alpha) increased bradykinin B(1) receptor mRNA, which peaked between 2 and 4 h, remaining elevated for 20 h. Binding of the bradykinin B(1) receptor selective ligand [3H]des-Arg(10)-kallidin, also increased, peaking at 4 h and remaining elevated for 20 h. The B(max) value for [3H]des-Arg(10)-kallidin rose from 280+/-102 fmol/mg (n=3) to 701+/-147 fmol/mg (n=3), but the K(D) value remained unaltered (control, 1.04+/-0.33 nM (n=3); interleukin-1 beta, 0.88+/-0.41 nM (n=3)). The interleukin-1 beta-induced [3H]des-Arg(10)-kallidin binding sites were functional receptors, as bradykinin B(1) receptor agonist-induced responses increased in treated cells. Bradykinin B(2) receptor mRNA and [3H]bradykinin binding were upregulated by interleukin-1 beta, but not TNF-alpha. The effect of interleukin-1 beta on bradykinin B(2) receptors was smaller than for bradykinin B(1) receptors. Cycloheximide prevented interleukin-1 beta-mediated increases in B(1) and B(2) binding, but not mRNA suggesting that de novo synthesis of a transcriptional activator was unnecessary.
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PMID:Regulation of bradykinin receptor gene expression in human lung fibroblasts. 1084 20

Seeds of the common ice plant (Mesembryanthemum crystallinum) germinate in distinct sub-populations over a time period of more than 4 weeks following imbibition. Distinguishing early (E)- and late (L)-germinating seeds is the expression of a homologue of the transcriptional activator VP1. The deduced amino acid sequence of ice plant VP1 (MVP1) is 39% identical (50% similar) to the sequence of the Arabidopsis VP1 homologue, ABI3. The amount of Mvp1 mRNA, transcribed from a single gene, is different in E and L seeds after water uptake. The levels of the Mvp1 transcripts are very low in immature and mature seeds and they increased during 6 days of imbibition. This expression profile of Mvp1 is different from known Vp1/ABI3-like genes in other plants. Cycloheximide (at 35 microM) abolishes the increase of Mvp1, and L seeds are turned into E seeds, which develop normally when the inhibitor is applied for a short time during imbibition. E seeds treated for the same time period are developmentally impaired and show no radicle elongation. We suggest that the presence and late disappearance of Mvp1 in L seeds is responsible for dormancy and after-ripening of late-germinating ice plant seeds.
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PMID:The expression of a Vp1-like gene and seed dormancy in Mesembryanthemum crystallinum. 1112 69