Identification and expression of a mouse muscle-specific CTL1 gene

Yuan, Zongfei; Wagner, Laura; Poloumienko, Arkadi; Bakovic, Marica

doi:10.1016/j.gene.2004.07.042

Cited by 39 publications

(57 citation statements)

References 38 publications

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“…To some extent, divergent regulation of the rat gene, which is different structurally from human and mouse genes in its distal promoter regions, could be expected. Essentially, this is in agreement with a more restricted expression of the rat gene in neuronal and intestinal tissues (60), as opposing to the broad expression of the mCTL1 and hCTL1 genes, at least at the mRNA level (73). No data are available for chimpanzee gene, and mRNA and protein expression data for the human form are described below, demonstrating a close relationship with the mouse gene.…”

Section: Human Ctl1 Choline Transportermentioning

confidence: 63%

“…The major difference is that the hCTL1 protein was uniformly abundant (Fig. 8A), whereas the mCTL1 protein was abundant only in skeletal muscle (73). The protein molecular mass calculated of the human and mouse cDNAs was similar and ϳ73 kDa (73).…”

Section: Human Ctl1 Choline Transportermentioning

confidence: 94%

“…Importantly, choline transporter-like (CTL) protein 1, a member of a second family of transporters distinct from CHT1, has been concurrently identified in the eel [Torpedo (t)CTL1 (40)], rat [rCTL1 (40)], mouse [mCTL1 (73)], and human [CDw92/hCTL1 (71)]. The physiological function of CTL proteins is less evident, and they have been suggested as candidate transporters for the provision of choline that is used in membrane lipid biosynthesis (40).…”

mentioning

confidence: 99%

“…The physiological function of CTL proteins is less evident, and they have been suggested as candidate transporters for the provision of choline that is used in membrane lipid biosynthesis (40). mCTL1 protein is predominantly expressed in skeletal muscle and is barely detectable in other tissues (73). rCTL1 mRNA is found solely in the colon, ileum, brain, and spinal cord (40,60), whereas hCTL1 protein, also named CDw92, is initially detected as a cell surface antigen in monocytic and dendritic cells (72).…”

mentioning

confidence: 99%

“…Tissue lysates of 30 g of total protein were denatured, resolved on 10% SDS-PAGE, and transferred to polyvinylidene difluoride membranes (Millipore). The membranes, including the human multiple-tissue INSTABlots, were blocked with 5% nonfat dry milk in Tris-buffered saline [TBS; 25 mM Tris ⅐ HCl (pH 7.4) and 0.15 M NaCl] for 1 h at room temperature and then incubated with VIM15 antibody (1:1,000 dilution) at 4°C overnight, as previously described (73). Afterward, membranes were extensively washed with TBS-Tween 20 (0.1%), incubated with horseradish peroxidase-conjugated goat anti-mouse antibody (1:10,000 dilution, Promega), and visualized by enhanced chemiluminescence (Sigma).…”

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confidence: 99%

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Genomic organization, promoter activity, and expression of the human choline transporter-like protein 1

Yuan

Tie

Tarnopolsky

et al. 2006

Physiological Genomics

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line transporter-like (CTL) proteins of the CTL1 family are novel transmembrane proteins implicated in choline transport for phospholipid synthesis. In this study, we characterized the 5Ј-flanking region of the human (h)CTL1 gene and examined some of the possible mechanisms of its regulation, including promoter activity, splicing, and expression. The transcription start site of the hCTL1 gene was mapped by 5Ј-rapid amplification of cDNA ends (RACE), and the presence of two splice variants, hCTL1a and hCTL1b, was investigated using isoform-specific PCR and 3Ј-RACE. The hCTL1 promoter region of ϳ900 bp was isolated from MCF-7 human breast cancer cells. The promoter was TATA-less and driven by a long stretch of GC-rich sequence in accordance with widespread expression of hCTL1 at both mRNA and protein levels. Deletion analyses demonstrated that a very strong promoter is contained within 500 bp of the transcription start site, and more upstream regions did not increase its activity. The core promoter that conferred the minimal transcription is within the Ϫ188/ϩ27-bp region, and its activity varied in human breast cancer and mouse skeletal muscle cells. Multiple motifs within the promoter regulatory region bound nuclear factors from both cultured cells and normal human skeletal muscle. The motifs within the three regions [S1 (Ϫ92/Ϫ61 bp), S2 (Ϫ174/Ϫ145 bp), and S3 (Ϫ289/Ϫ260 bp)] contained overlapping binding sites for hematopoietic transcription factors and ubiquitous transcription factors, in line with the expected gene function. Genomic analyses demonstrated a high conservation of hCTL1 and mouse CTL1 proximal promoters. Accordingly, mRNA profiles demonstrated that human splice variants were expressed ubiquitously, as demonstrated for the mouse transcripts; however, they differed from the profiles of rat CTL1 transcripts, which were more restricted to neurons and intestinal tissues. The shorter hCTL1b variant contained the cytosolic COOH-terminal motif L 651 KKR 654 for endoplasmic reticulum retrieval/retention. This retention signal was conserved in hCTL1b and rat and mouse CTL1b and is typical for transmembrane proteins of type 1 topology.choline transporter-like protein 1 promoters; gene expression THE MAJORITY OF CHOLINE is incorporated into phosphatidylcholine (PC) or proceeds through mitochondrial oxidation to betaine, thus entering the one-carbon methylation pool (74, 62), or is used in the production of the neurotransmitter acetylcholine (45). Interest in the factors that influence choline transport and metabolism has grown because of choline's association with neural tube defects (49, 51), memory development (75), Alzheimer's disease (53), homocysteine production (50), and inherited disorders of neuromuscular transmission (40, 78). The phosphorylation of intracellular choline by choline kinase and the subsequent production of CDP-choline, the main precursor of PC, by CTP:phosphocholine cytidylytransferase (Pcyt1) are the principal pathways for choline utilization and have been extensively studied and are ...

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Section: Human Ctl1 Choline Transportermentioning

confidence: 63%

Section: Human Ctl1 Choline Transportermentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Genomic organization, promoter activity, and expression of the human choline transporter-like protein 1

Yuan

Tie

Tarnopolsky

et al. 2006

Physiological Genomics

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Choline

Zeisel¹,

Corbin²

2012

Present Knowledge in Nutrition

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Choline transporter‐like proteins CTLs/SLC44 family as a novel molecular target for cancer therapy

Inazu

2014

Biopharm & Drug Disp

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Choline is essential for the synthesis of the major membrane phospholipid phosphatidylcholine (PC), the methyl donor betaine and the neurotransmitter acetylcholine (ACh). Elevated levels of choline and up-regulated choline kinase activity have been detected in various cancers. Thus, the intracellular accumulation of choline through choline transporters is the rate-limiting step in phospholipid metabolism and a prerequisite for cancer cell proliferation. Previous studies have demonstrated abnormalities in choline uptake and choline phospholipid metabolism in cancer cells using the imaging of cancer with positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). The aberrant choline metabolism in cancer cells is strongly correlated with their malignant progression. Using quantitative real-time PCR, the mRNA expression of choline transporters was measured, and it was found that choline transporter-like proteins CTLs/SLC44 family are highly expressed in various cancer cell lines. Choline uptake through CTLs is associated with cell viability, and the functional inhibition of CTLs could promote apoptotic cell death. Furthermore, nonneuronal cholinergic systems that include CTLs-mediated choline transport are associated with cell proliferation and their inhibition promotes apoptotic cell death in colon cancer, small cell lung cancer and human leukemic T-cells. The identification of this new CTLs-mediated choline transport system provides a potential new target for cancer therapy.

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Identification and expression of a mouse muscle-specific CTL1 gene

Cited by 39 publications

References 38 publications

Genomic organization, promoter activity, and expression of the human choline transporter-like protein 1

Genomic organization, promoter activity, and expression of the human choline transporter-like protein 1

Choline

Choline transporter‐like proteins CTLs/SLC44 family as a novel molecular target for cancer therapy

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