Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UID6 (Kruppel-like)
 147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wound repair in the liver induces altered gene expression in stellate cells (resident mesenchymal cells) in a process known as "activation." A zinc finger transcription factor cDNA, zf9, was cloned from rat stellate cells activated in vivo. Zf9 expression and biosynthesis are increased markedly in activated cells in vivo compared with cells from normal rats ("quiescent" cells). The factor is localized to the nucleus and the perinuclear zone in activated but not quiescent cells. Zf9 mRNA also is expressed widely in nonhepatic adult rat tissues and the fetal liver. The zf9 nucleotide sequence predicts a member of the Kruppel-like family with a unique N-terminal domain rich in serine-proline clusters and leucines. The human zf9 gene maps to chromosome 10P near the telomere. Zf9 binds specifically to a DNA oligonucleotide containing a GC box motif. The N-terminal domain of Zf9 (amino acids 1-201) is transactivating in the chimeric GAL4 hybrid system. In Drosophila schneider cells, full length Zf9 transactivates a reporter construct driven by the SV40 promoter/enhancer, which contains several GC boxes. A physiologic role for Zf9 is suggested by its transactivation of a collagen alpha1(I) promoter reporter. Transactivation of collagen alpha1(I) by Zf9 is context-dependent, occurring strongly in stellate cells, modestly in Hep G2 cells, and not at all in D. schneider cells. Our results suggest that Zf9 may be an important signal in hepatic stellate cell activation after liver injury.
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PMID:Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis. 968 9

Cystathionine beta-synthase (CBS) catalyzes the condensation of serine with homocysteine to form cystathionine and occupies a crucial regulatory position between the methionine cycle and transsulfuration. The human cystathionine beta-synthase gene promoters -1a and -1b are expressed in a limited number of tissues and are coordinately regulated with proliferation through a redox-sensitive mechanism. Site-directed mutagenesis, DNase I footprinting and deletion analysis of 5276 bp of 5' proximal -1b flanking sequence revealed that this region does not confer tissue-specific expression and that 210 bp of proximal sequence is sufficient for maximal promoter activity. As little as 32 bp of the -1b proximal promoter region is capable of driving transcription in HepG2 cells, and this activity is entirely dependent upon the presence of a single overlapping Sp1/Egr1 binding site. Co-transfection studies in Drosophila SL2 cells indicated that both promoters are transactivated by Sp1 and Sp3 but only the -1b promoter is subject to a site-specific synergistic regulatory interaction between Sp1 and Sp3. Sp1-deficient fibroblasts expressing both Sp3 and NF-Y were negative for CBS activity. Transfection of these cells with a mammalian Sp1 expression construct induced high levels of CBS activity indicating that Sp1 has a critical and indispensable role in the regulation of cystathionine beta-synthase. Sp1 binding to both CBS promoters is sensitive to proliferation status and is negatively regulated by Kruppel-like factors in co-transfection experiments suggesting a possible mechanism for the tissue specific regulation of cystathionine beta-synthase.
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PMID:The dominant role of Sp1 in regulating the cystathionine beta-synthase -1a and -1b promoters facilitates potential tissue-specific regulation by Kruppel-like factors. 1467 Sep 73