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Publications (3)5.53 Total impact

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    ABSTRACT: Functional mitochondria require up to 1000 proteins to function properly, with 99% synthesized as precursors in the cytoplasm and transported into the mitochondria with the aid of cytosolic chaperones and mitochondrial translocators (import components). Proteins to be imported are chaperoned to the mitochondria by the cytosolic heat shock protein (cHSP70) and are immediately pursued by Translocators of the Outer Membrane (TOMs), followed by transient interactions of the unfolded proteins with Translocators of the Inner Membrane (TIMs). In the present study, we describe a human gene, TOMM70A, orthologous to the yeast Tom70 import component. TOMM70A is ubiquitously expressed in human tissues, maps on chromosome 3q13.1-q13.2 and consists of 12 coding exons spanning over 37 kb. TOMM70A localizes in the mitochondria of COS-7 cells, and in organello import assays confirmed its presence in the Outer Mitochondrial membrane (OM) of rat liver mitochondria. TOMM70A could play a significant role in the import of nuclear-encoded mitochondrial proteins with internal targeting sites such as ADP/ATP carriers and the uncoupling proteins.
    Cell Communication & Adhesion 01/2002; 9(1):15-27. · 1.05 Impact Factor
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    ABSTRACT: The murine agouti related protein (mAGRP) is upregulated in obese and diabetic mice and stimulates hyperphagia when administered intracerebroventricularly (i.c.v.) or when overexpressed in transgenic mice. The human ortholog, hAGRP, has been isolated and has similar molecular and physiological properties. Here, we report the complete gene structure of the human AGRP gene and upstream regions with differential promoter activity. A polymorphism, A67T, in the third exon was identified but was not associated with obesity- or type 2 diabetes-related phenotypes. Putative binding sites for transcription factors were identified in the promoter of the gene including recognition sites for the signal transducers and activators of transcription (STATs) that may potentially mediate leptin's action in the hypothalamus. The upstream non-coding exon had significant promoter activity in a periphery- but not so in a hypothalamus-derived cell line, suggesting that it might contain the minimal promoter required for expression of the short transcript of hAGRP in the periphery.
    Gene 11/2001; 277(1-2):231-8. · 2.20 Impact Factor
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    ABSTRACT: The murine Agouti-Related Protein (mAGRP) is upregulated in obese and diabetic mice and can stimulate hyperphagia when overexpressed in transgenic models. Here we report upstream nucleotide sequences of the human hAGRP gene with putative recognition sites for transcription factors including a site for the STAT transactivators. A polymorphism (-38C-->T) was identified in the promoter region and the C/C genotype had significantly higher promoter activity and affinity for transcription factors as tested in periphery- and hypothalamus-derived cell lines. The polymorphic site could affect the expression levels of hAGRP and the high expressing C/C genotype was significantly associated with high BMI and type 2 diabetes in Africans.
    Biochemical and Biophysical Research Communications 09/2001; 287(2):568-73. · 2.28 Impact Factor