Genomic Structure of a Novel Chloride Channel Gene, CLIC2, in Xq28

Heiss, Nina S.; Poustka, Annemarie

doi:10.1006/geno.1997.4922

Cited by 69 publications

(51 citation statements)

References 16 publications

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“…mc3s5 Protein Is Homologous to a Family of Chloride Channel Proteins-The protein encoded by the ORF also shared high similarity with the three chloride channel proteins present in the data base, bovine p64 (24), human NCC27 or CLIC1 (25,26), and CLIC2 (27). All three proteins are members of a new family of CLICs (Fig.…”

Section: P53-regulated Mitochondrial Chloride Channelmentioning

confidence: 89%

p53 and Tumor Necrosis Factor α Regulate the Expression of a Mitochondrial Chloride Channel Protein

Fernández‐Salas

Sagar

Cheng

et al. 1999

Journal of Biological Chemistry

128

148

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A novel chloride intracellular channel (CLIC) gene, clone mc3s5/mtCLIC, has been identified from differential display analysis of differentiating mouse keratinocytes from p53؉/؉ and p53؊/؊ mice. The 4.2-kilobase pair cDNA contains an open reading frame of 762 base pairs encoding a 253-amino acid protein with two putative transmembrane domains. mc3s5/mtCLIC protein shares extensive homology with a family of intracellular organelle chloride channels but is the first shown to be differentially regulated. mc3s5/mtCLIC mRNA is expressed to the greatest extent in vivo in heart, lung, liver, kidney, and skin, with reduced levels in some organs from p53؊/؊ mice. mc3s5/mtCLIC mRNA and protein are higher in p53؉/؉ compared with p53؊/؊ basal keratinocytes in culture, and both increase in differentiating keratinocytes independent of genotype. Overexpression of p53 in keratinocytes induces mc3s5/mtCLIC mRNA and protein. Exogenous human recombinant tumor necrosis factor ␣ also up-regulates mc3s5/mtCLIC mRNA and protein in keratinocytes. Subcellular fractionation of keratinocytes indicates that both the green fluorescent protein-mc3s5 fusion protein and the endogenous mc3s5/mtCLIC are localized to the cytoplasm and mitochondria. Similarly, mc3s5/mtCLIC was localized to mitochondria and cytoplasmic fractions of rat liver homogenates. Furthermore, mc3s5/mtCLIC colocalized with cytochrome oxidase in keratinocyte mitochondria by immunofluorescence and was also detected in the cytoplasmic compartment. Sucrose gradient-purified mitochondria from rat liver confirmed this mitochondrial localization. This represents the first report of localization of a CLIC type chloride channel in mitochondria and the first indication that expression of an organellular chloride channel can be regulated by p53 and tumor necrosis factor ␣.The multiple functions now ascribed to the p53 tumor suppressor gene include cell cycle control, DNA repair, senescence, differentiation, and apoptosis (reviewed in Refs. 1-3). p53 exerts part of its biological function by activating or repressing the transcription of several target genes (2, 4, 5). p53 is particularly important in the skin because it is frequently mutated in preneoplastic and neoplastic human skin lesions (6), and loss of p53 enhances malignant progression of experimentally induced murine skin tumors (7). In keratinocytes, p53-dependent transcriptional activity increases in association with terminal differentiation (8). However, the skin of p53-deficient mice appears to be normal in vivo (9), and the expression of differentiation markers by p53Ϫ/Ϫ keratinocytes in vitro cannot be distinguished from that of wild-type (8). This implies that p53 is dispensable for normal skin development and differentiation. However, deletion of one or both p53 alleles enhances the establishment of immortal keratinocyte cell lines in vitro (10), suggesting that p53 could participate in keratinocyte mortality in a more subtle way, not involving expression of the major differentiation-related markers. To detect such a con...

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Section: P53-regulated Mitochondrial Chloride Channelmentioning

confidence: 89%

p53 and Tumor Necrosis Factor α Regulate the Expression of a Mitochondrial Chloride Channel Protein

Fernández‐Salas

Sagar

Cheng

et al. 1999

Journal of Biological Chemistry

128

148

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“…Human CLIC1 was identified as a putative nuclear membrane Cl − channel [19]. Human CLIC2 is a hypothetical protein encoded by the putative gene XAP121 [25]. The cDNA encoding human CLIC3, postulated like CLIC1 to be a nuclear membrane Cl − channel protein, was cloned during a yeast two-hybrid screen [20] for partners interacting with the C-terminal domain of an atypical mitogen-activated protein kinase, ERK-7.…”

Section: Introductionmentioning

confidence: 99%

Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Suginta

Karoulias

Aitken

et al. 2001

Biochemical Journal

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Mammalian chloride intracellular channel (CLIC) (p64-related) proteins are widely expressed, with an unusual dual localization as both soluble and integral membrane proteins. The molecular basis for their cellular localization and ion channel activity remains unclear. To help in addressing these problems, we identified novel rat brain CLIC4 (p64H1) binding partners by affinity chromatography, mass spectrometric analysis and microsequencing. Brain CLIC4 binds dynamin I, α-tubulin, β-actin, creatine kinase and two 14-3-3 isoforms ; the interactions are confirmed in i o by immunoprecipitation. Gel overlay and reverse pull-down assays indicate that the binding of CLIC4 to dynamin I and 14-3-3ζ is direct. In HEK-293 cells, biochemical and immunofluorescence analyses show partial co-localization of

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“…P64 has subsequently been discovered to be a member of a family of related proteins which to date includes 7 members (5)(6)(7)(8)(9)(10)(11)(12)(13). This family has been named the CLIC family for chloride intracellular channel (9).…”

mentioning

confidence: 99%

“…This family has been named the CLIC family for chloride intracellular channel (9). Chloride channel activity has been attributed to several of these p64 homologs (5,7,10,11,13).…”

mentioning

confidence: 99%

Regulation of the Bovine Kidney Microsomal Chloride Channel p64 by p59 , a Src Family Tyrosine Kinase

Edwards

Kapadia

2000

Journal of Biological Chemistry

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p64 is a chloride channel of intracellular membranes which is present in regulated secretory vesicles. Mechanisms by which the p64 channel could be regulated are largely unknown. p59fyn is a non-receptor tyrosine kinase of the Src family that has been implicated in a variety of intracellular signaling events. The N-terminal portion of p64 has several potential binding sites for Src family SH2 domains. In this paper, we demonstrate that p64 becomes tyrosine phosphorylated when co-expressed with p59 fyn in HeLa cells. We show that co-expression of p64 with p59 fyn renders p64 a ligand for the SH2 domain of p59 fyn and this SH2 binding is eliminated by treating p64 with alkaline phosphatase. Using sitedirected mutagenesis, we find that tyrosine 33 in the p64 sequence is necessary for SH2 binding. We also characterized p64-p59 fyn interactions using native material from bovine kidney. We found that a small fraction of native kidney p64 can bind Fyn SH2 in vitro. Immunoprecipitation of p64 from solubilized kidney membranes yields a kinase activity with the same mobility by SDSpolyacrylamide gel electrophoresis as authentic bovine p59fyn . Finally, we demonstrate that co-expression of p64 and p59 fyn in HeLa cells results in enhanced p64-associated chloride channel activity.

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Genomic Structure of a Novel Chloride Channel Gene, CLIC2, in Xq28

Cited by 69 publications

References 16 publications

p53 and Tumor Necrosis Factor α Regulate the Expression of a Mitochondrial Chloride Channel Protein

p53 and Tumor Necrosis Factor α Regulate the Expression of a Mitochondrial Chloride Channel Protein

Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Regulation of the Bovine Kidney Microsomal Chloride Channel p64 by p59 , a Src Family Tyrosine Kinase

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