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)

Water channel aquaporin-1 (AQP1) is expressed in erythrocytes and various epithelia and endothelia. To study AQP1 gene regulation, human cell lines were screened for inducible AQP1 expression. Human erythroleukemia HEL cells showed AQP1 transcript expression on RNase protection assay. After butyrate-induced erythroid differentiation, AQP1 transcript expression increased strongly, producing water-permeable cells with plasma membrane localization of immunoreactive AQP1. In addition, a clonal subline of K562 cells [K562(S)] showed strong butyrate-induced expression of functional AQP1. A 1.8-kb DNA fragment of the 5' flanking region of the human AQP1 gene was isolated, sequenced, and analyzed functionally by the CAT reporter assay. The AQP1 promoter contained TATA and CCAAT boxes; Sp1, AP1, AP2, and E-box elements; and erythrocyte-specific CACCC and Kruppel-like (CCCCACCCA) elements. AQP1 promoter activity was more than 24-fold higher in HEL and K562(S) cells than in nonerythroid (HeLa) cells, indicating the presence of erythroid-specific factors. In K562(S) cells, CAT activities for promoter fragments to bp +23 [relative to beta-gal and normalized to 100% for the plasmid CP-282 (bp -282 to +23)] were 22 (-1779), 73 (-1402), 61 (-1129), 31 (-789), 87 (-487), 100 (-282), 73 (-229), 52 (-152), and 60% (-79). After butyrate-induced differentiation, CAT activities were stimulated approximately 10-fold for constructs -229/+23 and longer, compared to approximately 5-fold for -152/+23 and -79/+23; glucocorticoids did not affect CAT activities. These results suggest a basis for erythroid-specific AQP1 expression and the presence of a butyrate-response sequence involved in inducible AQP1 regulation in erythroleukemia cells.
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PMID:Isolation of the human aquaporin-1 promoter and functional characterization in human erythroleukemia cell lines. 948 Jul 47

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

Erythroid Kruppel-like Factor (EKLF) is an erythroid-specific transcription factor that plays a critical role in gamma- to beta-globin gene switching during development. To identify essential domains required for EKLF transactivation function, we cotransfected a human erythroleukemia cell line (K562) with a locus control region gamma/Luc-beta/Cat reporter and an EKLF expression vector. In this assay EKLF mediates a 500-fold induction of beta/CAT expression compared with controls. To map essential transactivation domains, progressive NH(2)-terminal and internal deletion mutants of EKLF were constructed. All EKLF mutants were expressed at wild-type levels, localized to the nucleus, and bound DNA. When mutant EKLF proteins were tested for beta/CAT activation, a novel transactivation domain was identified. This novel domain, encompassing amino acids (aa) 140-358, is sufficient for maximal beta/CAT activation. An 85-amino acid subdomain within this region (aa 140-225) is essential for its activity. Interestingly, this central transactivation subdomain is functionally redundant with the amino-terminal domain (aa 1-139). Thus, EKLF possesses at least two potent transactivation domains that appear to function in a redundant manner.
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PMID:Novel transactivation domain in erythroid Kruppel-like factor (EKLF). 1109 87

The dual oxidases (DUOX1 and DUOX2) are NADPH-dependent hydrogen peroxide-producing enzymes that are reported to function in a physiological capacity and as a component of the mucosal immune response. We have previously reported increased expression of the DUOX2 gene in the gut mucosa of sheep in response to gastrointestinal nematode (GIN) challenge. In this paper, we report the cloning of the full-length ovine DUOX2 transcript, using a PCR based strategy. The ovine DUOX2 transcript includes an ORF of 4644 bases, and encodes a protein with 97% identity to the bovine sequence. We also cloned a fragment of DUOX1 (encompassing nucleotides 2692-2829), and the proximal promoter sequence of DUOX2. Through analysis of sequence data we have confirmed that DUOX1 and DUOX2 are co-located in a head to tail arrangement conserved across many species. Alignment of the sequences to the ovine genome predicts a location of this gene cluster on ovine chromosome 7. We quantified the expression of ovine DUOX1 and DUOX2 transcripts in 24 different sheep tissues, and discovered tissue specific expression signatures. DUOX2 was found to be most highly expressed in tissues of the gastrointestinal tract, while expression of DUOX1 predominated in the bladder. Rapid amplification of cDNA ends (RACE) analysis identified the existence of multiple 5' UTR variants in DUOX2, ranging in size from 32 to 242 nucleotides, with 3 distinct transcribed regions. Real time PCR quantification of the DUOX2 UTR variants revealed that these were differentially expressed between tissues, and at various stages of the response to GIN parasite infection. The collective evidence suggested a complex regulation of DUOX2, prompting a bioinformatic analysis of the proximal promoter regions of ovine DUOX2 to identify potential transcription factor binding sites (TFBS) that may explain the differences in the observed expression of the transcript variants of DUOX2. Possible transcription factor families that may regulate this process were identified as Kruppel-like factors (KLF), ETS-factors, erythroid growth receptor factors (EGRF) and myogenic differentiation factors (MYOD).
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PMID:Molecular cloning and characterisation of ovine dual oxidase 2. 2246 29