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

Lung Kruppel-like factor (LKLF) is a member of the Kruppel-like family of zinc finger transcription factors and is closely related to erythroid kruppel-like factor (EKLF), which is necessary for beta-globin gene expression. While EKLF is expressed exclusively in erythroid cells, LKLF is expressed temporally during early embryonic development and predominantly in the adult mouse lung. To understand the role this novel transcription factor plays in development as well as tissue differentiation and function, animals lacking LKLF were produced using gene targeting technology. Mice lacking LKLF die in utero between day 11.5 and 13.5 of embryonic life and exhibit retarded growth, craniofacial abnormalities, abdominal bleeding and signs of anaemia. Although the yolk sac erythropoiesis is normal in mutant embryos, in vitro fetal liver cultures of these embryos fail to give rise to erythroid cells. Expression of other erythroid specific genes such as EKLF, GATA1 and GATA3 is unaltered in these animals. These findings demonstrate the LKLF function is indispensable during normal embryonic development, and although both LKLF and EKLF recognize common DNA motifs, they do not substitute for each other.
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PMID:Loss of LKLF function results in embryonic lethality in mice. 985 12

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.
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PMID:Cell-specific transcription of leukotriene C(4) synthase involves a Kruppel-like transcription factor and Sp1. 1072 37

Kruppel-like Factor 2 [KLF2, also called lung Kruppel-like factor (LKLF)] is a transcription factor shown to be necessary for the maintenance of naive T cells. KLF2 is expressed in both naive and memory cells, and is proposed to promote quiescence in these populations. During T cell stimulation, both KLF2 protein and mRNA are down-regulated, and loss of KLF2 appears to be critical for full T cell activation. It is unclear, however, how KLF2 expression is maintained in naive T cells. Recently it was proposed that IL-7, which is known to promote KLF2 re-expression in antigen-stimulated T cells, may also induce KLF2 expression in naive T cells. Here we address this issue by comparing the impact of IL-7 on KLF2 expression in naive and activated T cells. Use of bcl-2 transgenic T cells allowed us to uncouple the requirements for IL-7 in preserving naive T cell survival from its role in maintaining KLF2 expression. Our data demonstrates that IL-7 signals are not required for KLF2 maintenance in naive T cells, suggesting that this cytokine has distinct effects on KLF2 expression in naive versus activated T cells.
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PMID:Differential role for IL-7 in inducing lung Kruppel-like factor (Kruppel-like factor 2) expression by naive versus activated T cells. 1456 32

Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types. Deficiency in Kruppel-like factor (KLF) 2 (also known as LKLF) leads to a massive loss of the peripheral T-cell pool, suggesting KLF2 regulates T-cell quiescence and survival. Here we show, however, that KLF2 is essential for T-cell trafficking. KLF2-deficient (Klf2-/-) thymocytes show impaired expression of several receptors required for thymocyte emigration and peripheral trafficking, including the sphingosine-1-phosphate (S1P) receptor S1P1, CD62L and beta7 integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P1--a receptor that is critical for thymocyte egress and recirculation through peripheral lymphoid organs. Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues.
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PMID:Kruppel-like factor 2 regulates thymocyte and T-cell migration. 1685 90

Statins upregulate endothelial thrombomodulin (TM) by mechanisms that involve members of the Kruppel-like factor family. Although Kruppel-like factors are unequivocally implicated in this process, experimental evidence points to additional mechanisms. Deletion/mutation analysis of reporter constructs was used to demonstrate that mutation of the SP1/Kruppel-like factor element in the TM promoter only partially abolishes statin-induced TM upregulation, whereas simultaneous mutation of relevant heat shock elements and SP1/Kruppel-like factor element completely prevents statin-induced TM upregulation, thus demonstrating a role for heat shock factors (HSFs). We further identified the pathway by which statins increase binding of HSF1 to heat shock elements in the TM promoter. Specifically, statins caused NO-dependent dissociation of HSF1 from heat shock protein 90, nuclear translocation of HSF1, and binding to heat shock elements in the TM promoter. Statins also decreased nuclear content of the HSF1 chaperone 14-3-3beta. In addition to reducing TM upregulation, inhibition of HSF1 reduced statin-induced upregulation of tissue plasminogen activator, whereas downregulation of thrombomospondin, plasminogen activator inhibitor 1, or connective tissue growth factor was unaffected. Knockdown of 14-3-3beta or inhibition of HSF1 phosphorylation enhanced the effect of statins on TM and tissue plasminogen activator, but did not influence thrombomospondin, plasminogen activator inhibitor 1, or connective tissue growth factor. These data demonstrate that HSF1 is involved in statin-induced regulation of TM. They also suggest that analogous mechanisms may apply to genes that are upregulated by statins, but not to downregulated genes. These results may have broad implications and suggest the use of heat shock protein modulators to selectively regulate pleiotropic statin effects.
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PMID:Involvement of heat shock factor 1 in statin-induced transcriptional upregulation of endothelial thrombomodulin. 1870 84