Disease relevance of CAR1

• Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying lambda hARG6 cDNA insert [1].
• To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, we isolated cDNA clones for human liver arginase [1].
• Arginine catabolism in the phototrophic bacterium Rhodobacter capsulatus E1F1. Purification and properties of arginase [2].

High impact information on CAR1

• On the other hand, the cargA + Oh-1 and cargA + Oh-2 mutations, leading to a constitutive and mating-type dependent arginase synthesis, were identified as insertions [3].
• This result suggests either a surprisingly large arginase regulatory region or an indirect influence of the Ty1 element on gene expression over long distances [3].
• The nitrogen status for other nitrogen-responsive processes such as catabolic gene expression and sporulation also is signaled by this tRNA: mutant cells inappropriately induce the nitrogen-repressed gene CAR1 and undergo precocious sporulation in nitrogen-rich media [4].
• The URS1-TRK2 sequence (5'-AGCCGCACG-3') shares six nucleotides with the ubiquitous URS1 element (5'-AGCCGCCGA-3'), and the protein species binding URS1-CAR1 (URSF) is capable of binding URS1-TRK2 in vitro [5].
• This was not observed, however, when it was situated downstream of a heterologous CYC1 upstream activation sequence indicating that URS function is specifically neutralized by cis-acting elements associated with CAR1 induction [6].

Chemical compound and disease context of CAR1

• In order to probe the chemistry of N-bromosuccinimide inactivation and the role of tryptophan residues in catalysis, the two tryptophan residues of rat liver arginase, Trp122 and Trp164, have been separately mutated to phenylalanine using site-directed mutagenesis of the protein expressed in Escherichia coli [7].

Biological context of CAR1

• The nucleotide sequence of this latter region is very similar to essential sequences within the URS elements from the yeast CAR1 and SSA1 genes, respectively [8].
• The yeast UME6 gene product is required for transcriptional repression mediated by the CAR1 URS1 repressor binding site [9].
• Arginase (CAR1) gene expression in Saccharomyces cerevisiae is induced by arginine [10].
• Similar sequences situated upstream of ARG5,6 and ARG3 and reported to negatively regulate their expression are able to functionally substitute for the CAR1 UASI elements and mediate reporter gene expression [10].
• The 5' regulatory region of CAR1 contains four separable regulatory elements--two inducer-independent upstream activation sequences (UASs) (UASC1 and UASC2), an inducer-dependent UAS (UASI), and an upstream repression sequence (URS1) which negatively regulates CAR1 and many other yeast genes [10].

Anatomical context of CAR1

• We conclude that arginase deficiency in the red blood cells and probably in the liver is inherited in an autosomal recessive manner and is responsible for the clinical syndrome in this patient [11].
• Arginase (EC 3.5.3.1) and ornithine delta-aminotransferase (E.C. 2.6.1.13) were found to reside in cytosol [12].
• The CGH-1/CAR-1 interaction is conserved in Drosophila oocytes [13].
• Here, we describe a predicted RNA-binding protein, CAR-1, that associates with CGH-1 and Y-box proteins within a conserved germline RNA-protein (RNP) complex, and in cytoplasmic particles in the gonad and early embryo [13].
• We conclude that CAR-1 is of critical importance for oogenesis, that the association between CAR-1 and CGH-1 has been conserved, and that the regulation of physiological germ cell apoptosis is specifically influenced by certain functions of the CGH-1/CAR-1 RNP complex [13].

Associations of CAR1 with chemical compounds

• A single URS1 site mediates repression of CAR1 arginine-independent upstream activator site (UAS) activity in the absence of arginine and the presence of a poor nitrogen source (a condition under which the inducer-independent Gln3p can function in association with the UASNTR sites) [14].
• URS1 is known to be a repressor binding site in Saccharomyces cerevisiae that negatively regulates expression of many genes including CAR1 (arginase), several required for sporulation, mating type switching, inositol metabolism, and oxidative carbon metabolism [9].
• We show that Gln3p activates CAR1 expression through the GATAA sequences in the absence of an optimal nitrogen source, such as ammonia, glutamine or asparagine [15].
• Expression of the arginase (CAR1) gene in Saccharomyces cerevisiae is induced by arginine or its analog homoarginine [16].
• First, the yeast strain was transformed with plasmid pCAT2 (delta car1 SMR1), and strains heterozygous for CAR1 gene were isolated on sulfometuron methyl plates [17].

Physical interactions of CAR1

• Our in vitro binding experiments confirm the presence of MCM1 in the protein complex interacting with the promoters of the catabolic CAR1 and CAR2 genes [18].
• The higher-affinity ABF-1 binding site upstream of CAR1 was an effective competitor of the HMRE, ARS1 B domain, and COR2-GFI binding sequences for protein binding [19].
• Ornithine carbamoyltransferase of Saccharomyces cerevisiae is subjected to an enzymatic regulation of its anabolic activity when it is bound to the inducible catabolic arginase as described earlier [20].

Regulatory relationships of CAR1

• Within this negative region a ten base-pair sequence was detected that shows high homology to a sequence located within a negative control region of the CYC1 gene and some homology to the negative control elements of the S. cerevisiae CAR1 and CAR2 genes [21].

Other interactions of CAR1

• The products of three genes named CARGRI, CARGRII, and CARGRIII were shown to repress the expression of CAR1 and CAR2 genes, involved in arginine catabolism [22].
• Participation of RAP1 protein in expression of the Saccharomyces cerevisiae arginase (CAR1) gene [23].
• Similarly we have measured the mRNA levels for two genes subject to the arginine specific regulation: ARG3 and CAR1, the former gene belongs to the arginine anabolic pathway and the latter to the arginine catabolic one [24].
• We demonstrate here that these gene products, along with that of the MCM1 gene, are required for the inducer-dependent USAI-A, UASI-B and UASI-C elements to function but they are not required for operation of inducer-independent CAR1 UASC1 or UASC2 [25].
• CAR1 and YGP1 genes are not specifically induced under conditions of nitrogen starvation [26].

Analytical, diagnostic and therapeutic context of CAR1

• CAR1 DNA fragments containing the yeast CAR1 gene sequences from the transcription initiation site (-49) or translation initiation site (+1) to the +501 region were amplified using PCR and inversely fused to the yeast CYC1 promoter on the yeast YIp5 plasmid [27].
• Molecular cloning, DNA structure, and RNA analysis of the arginase gene in Saccharomyces cerevisiae. A study of cis-dominant regulatory mutations [3].
• A molecular stoichiometry in the complex of one molecule of OTCase to one molecule of arginase was verified using transmission electron microscopy [28].
• Genetic engineering of a sake yeast producing no urea by successive disruption of arginase gene [17].
• Electron microscopic studies employing negative staining, rotary shadowing, and unidirectional shadowing have revealed the subunit architecture of ornithine transcarbamoylase and arginase from Saccharomyces cerevisiae [29].

References