Disease relevance of PACRG

• Genetic analysis of parkin co-regulated gene (PACRG) in patients with early-onset parkinsonism [1].
• Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia [2].
• Abnormal methylation of the common promoter of PARK2 and PACRG was observed in 26% of patients with acute lymphoblastic leukemia and 20% of patients with chronic myelogenous leukemia (CML) in lymphoid blast crisis, but not in ovarian, breast, lung, neuroblastoma, astrocytoma or colon cancer cells [2].
• In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG [3].
• PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever [4].

High impact information on PACRG

• With respect to genome-wide screens, a major breakthrough has been reported this year; variants in the regulatory region shared by PARK2 and PACRG have been identified as being common risk factors for leprosy [5].
• Deletion of the Parkin coregulated gene causes male sterility in the quaking(viable) mouse mutant [6].
• The Gl 8 protein variant is found in Ashkenazi Jews (gene frequency around .008) but not in the general white, black, or Japanese populations [7].
• Glup knockdown attenuated the formation of Pael-R inclusions, which resulted in the promotion of cell death with extensive vacuolization [8].
• Moreover, Glup turned out to be a component of Lewy bodies in Parkinson's disease cases [8].

Chemical compound and disease context of PACRG

• Deletion of the parkin and PACRG gene promoter in early-onset parkinsonism [9].

Biological context of PACRG

• Database analysis identified highly conserved homologs of PACRG encoded by the mouse and Drosophila genomes, and Northern analysis demonstrated that PACRG and parkin were co-expressed in many tissues, including brain, heart and muscle [10].
• PARK2 is linked to a novel described PACRG gene by a bidirectional promoter containing a defined CpG island in its common promoter region [2].
• Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy [3].
• The Parkin co-regulated gene product, PACRG, is an evolutionarily conserved axonemal protein that functions in outer-doublet microtubule morphogenesis [11].
• Association study of major risk single nucleotide polymorphisms in the common regulatory region of PARK2 and PACRG genes with leprosy in an Indian population [12].

Anatomical context of PACRG

• We have studied the role of promoter hypermethylation in the regulation of PARK2 and PACRG expression in different tumor cell lines and primary patient samples [2].
• Our results provide the first evidence for PACRG function within the axoneme, where we suggest that PACRG acts to maintain functional stability of the axonemal outer doublets of both motile and sensory cilia and flagella [11].
• Enzyme assay of lysates of a girl's lymphocytes or cultured fibroblasts showed little residual activity and a normal beta Gl-specific mRNA level, as revealed by Northern-blot analysis [13].
• RT-PCR showed that the Gl-NOS mRNA was present in testis, ovary, gill, eyestalk neural ganglia, thoracic ganglion and Y-organ [14].

Associations of PACRG with chemical compounds

• We have tentatively named this novel gene Parkin co-regulated gene, or PACRG [10].
• The Gl proteins of several subjects were typed by two polyacrylamide gel electrophoresis (PAGE) systems: acid-lactate PAGE followed by staining with the periodic acid-Schiff reagent and sodium dodecyl sulfate-PAGE followed by electrophoretic transfer and staining with amido black or concanavalin A [15].
• Gl-NOS had single amino acid differences in all three highly conserved FAD-binding sequences, which distinguished it from other NOS sequences [14].

Other interactions of PACRG

• One was 1,002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B [16].
• Analysis of mutants depleted in particular flagellar and basal body proteins [gamma-tubulin, delta-tubulin, Parkin co-regulated gene product (PACRG) or the paraflagellar rod protein PFR2] allowed a dissection of the mechanisms for central pair constraint [17].

Analytical, diagnostic and therapeutic context of PACRG

• Immunohistochemistry confirmed that the Gl-NOS protein was expressed in Y-organ, ovary and gill [14].
• Nested reverse transcription-polymerase chain reaction (RT-PCR) and 5' and 3' rapid amplification of cDNA ends (RACE) PCR generated a full-length cDNA sequence (3982 bp) of land crab NO synthase (Gl-NOS) from molting gland (Y-organ) and thoracic ganglion mRNA [14].

References