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

Accumulating evidence supports the hypothesis that tumor-suppressor p53 can act as a transcriptional activator. Insertion of high-affinity p53 DNA binding sites upstream of a promoter yields a p53-responsive vector. Chimeric proteins fusing p53 and the GAL4 DNA-binding domain demonstrate the presence of a transcriptional activating domain in the N-terminus of p53. GAL4-p53 chimeras constructed using naturally occurring p53 mutations at either codon 141 (Tyr-141) or 175 (His-175) of p53 had little ability to activate the reporter gene; in contrast, mutations at either codon 248 (Trp-248) or 273 (His-273) produced greater transcriptional activities than did wild-type p53. GAL4 chimeras can be used to analyse interactions between different domains of p53 and between different p53 alleles; a DNA binding site is defined, and a simple measurement can be made of function. We had expected that coexpression of GAL4 chimeras and p53 alleles would squelch transcriptional activation downstream of GAL binding sites. Surprisingly, coexpression of either p53 (Trp-248) or (His-273) with the GALA-p53 (wild-type, His-273, Trp-248, His-175, Tyr-141) effectors conferred an increase in transcriptional activation as compared with the effector alone. Oligomerization of p53 alleles with GAL4-p53 chimeras could underlie this effect, leading to an increase in transcription-activating motifs near the promoter. To test this possibility, we constructed a GAL4-p53 C-terminal chimera with p53 residues 160-393, lacking the transcriptional activating domain but retaining regions believed to be important in p53 oligomerization. Neither GAL4-p53 (C-terminus) nor p53 expression vectors were able to transactivate G5E1B-CAT alone. Both p53 (His-273) and (Trp-248) co-expressed with GAL4-p53 (C-terminus) were able to transactivate the G5E1B-CAT reporter gene; in contrast, p53 (Tyr-141) was not able to activate transcription. p53 (Tyr-141/His-273) behaved as a dominant negative mutant and inhibited the ability of the combination of p53 (His-273) and GAL4-p53 (C-terminus) to stimulate the reporter gene. Double immunoprecipitation by sequentially using GAL4 and p53 antibodies showed that p53 (His-273) and (Tyr-141/His-273), but not p53 (Tyr-141), can efficiently oligomerize in vivo to the C-terminal region of p53. Transcriptional activating function of p53 may be modulated by oligomerization; some mutations, such as His-273 and Trp-248, participate in these functions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mutant p53 proteins have diverse intracellular abilities to oligomerize and activate transcription. 851 Sep 27

The Hrp type III secretion system (TTSS) is essential for the pathogenicity of Ralstonia solanacearum on host plants. Hrp TTSS is a specialized secretion system that injects virulence proteins, the so-called type III effector proteins, into plant cells. In R. solanacearum, the expression of Hrp TTSS-related genes is regulated by an AraC-type transcriptional activator, HrpB. We have identified 30 hrpB-regulated hpx (hrpB-dependent expression) genes and three well-known hrpB-regulated genes, popA, popB and popC, as candidate effector genes in R. solanacearum strain RS1000. In this study, we newly cloned 11 additional candidate effector genes that share homology with known hpx genes from R. solanacearum RS1000. Using a Cya reporter system, we investigated the translocation of these 44 gene products into plant cells via the Hrp TTSS and identified 34 effector proteins. These include three effector families composed of more than four members, namely the Hpx4, Hpx30 and GALA families. The Hpx30 family effectors are 2200-2500 aa in size and appear to be the largest class of effector proteins among animal- and plant-pathogenic bacteria. Members of this family contain 12-18 tandem repeats of a novel 42 aa motif, designated SKWP repeats.
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PMID:Identification of novel Ralstonia solanacearum type III effector proteins through translocation analysis of hrpB-regulated gene products. 1940 97