Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:Q9UID6 (
Kruppel-like
)
147
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We isolated a cDNA encoding a human homologue of ZF5 (hZF5), which has five
Kruppel-like
C2H2 type zinc fingers at carboxyl terminus and the BTB/POZ (poxvirus and zinc finger) at the amino terminus, using autoimmune sera from a patient with overlap syndrome (dermatomyositis and scleroderma). Sequencing of the entire cDNA revealed an open reading frame (ORF) of 1349 bp with a deduced protein sequence of 449 amino acid residues and a calculated molecular weight of 51.3 kDa. The deduced amino acid sequence of hZF5 is highly homologous to mouse ZF5 (99.3% identity). Immunofluorescence studies revealed that HA-tagged hZF5 transiently expressed in
COS
-7 cells showed the nuclear dot pattern in the BTB/POZ domain-dependent manner.
...
PMID:Expression cloning and intracellular localization of a human ZF5 homologue. 917 79
Leukotriene C(4) synthase (LTC(4)S) is responsible for the biosynthesis of cysteinyl leukotrienes that participate in allergic and asthmatic inflammation. We analyzed 2.1 kilobases of the 5'-flanking region of the human LTC(4)S gene, which contains three DNase I hypersensitivity sites, for its transcriptional activity when fused to a promoterless and enhancerless luciferase gene. Deletion analysis revealed a nonspecific basal promoter region between nucleotides -122 and -56 upstream of the translation start site which contains a consensus Sp1 binding site and a putative initiator element (Inr) and cell-specific enhancer regions further upstream. A single mutation of either the Sp1 binding site between nucleotides -120 and -115 or the Inr (CAGAC) between nucleotides -66 and -62 reduced the expression of the reporter gene by approximately 60%, whereas double mutations decreased the expression by approximately 80%. The incubation of nuclear extracts from THP-1 and K562 cells with a (32)P-labeled oligonucleotide containing the Sp1 site or the Inr sequence gave gel-shifted complexes that were blocked by their respective cold oligonucleotides, and antisera specific for Sp1 and Sp3 provided supershifts for the former. Linker-scanning mutations of a cell-specific regulatory region revealed that mutations from nucleotides -165 to -125 reduced reporter activity. This region contains a tandem CACCC repeat (at nucleotides -149 to -145 and -139 to -135). An oligonucleotide containing the distal CACCC motif was gel shifted by THP-1 cell nuclear extract and was supershifted by antisera to Sp1 and Sp3. Cotransfection of an Sp1 expression plasmid into Drosophila SL2 cells with a -228 to -3 LTC(4)S reporter construct transactivated the reporter gene, whereas mutations at the CACCC repeat region reduced Sp1 transactivation by approximately 66%. Similarly, the Kruppel-like factor Zf9/CPBP (core promoter-binding protein) transactivated the -228 construct in
COS
cells but not its CACCC mutant construct. These findings indicate the involvement of Sp1 and an Inr in non-cell-specific regulation and a
Kruppel-like
transcription factor and Sp1 in the cell-specific regulation of the LTC(4)S gene. These are the first such analyses of a member of a newly recognized superfamily of membrane-associated proteins involved in eicosanoid and glutathione metabolism, which contains key proteins involved in the generation of both prostanoids and cysteinyl leukotrienes.
...
PMID:Cell-specific transcription of leukotriene C(4) synthase involves a Kruppel-like transcription factor and Sp1. 1072 37