A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carot...

Eukaryotic translation initiation factor 5A (eIF-5A, older nomenclature, eIF-4D) is a highly conserved protein that contains the unusual amino acid hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine). The biosynthesis of hypusine occurs posttranslationally in only this protein by modification of a single lysine residue (Lys50 in the human eIF-5A precursor). The basis for the specificity of this...

Previously, we have shown that Wnt-5a strongly regulates dopaminergic neuron differentiation by inducing phosphorylation of Dishevelled (Dvl). Here, we identify additional components of the Wnt-5a-Dvl pathway in dopaminergic cells. Using in vitro gain-of-function and loss-of-function approaches, we reveal that casein kinase 1 (CK1) delta and CK1epsilon are crucial for Dvl phosphorylation by non...

The 5-HT(5A) receptor is the least understood serotonin (5-HT) receptor. Here, we electrophysiologically identify and characterize a native 5-HT(5A) receptor current in acute ex vivo brain slices of adult rodent prefrontal cortex. In the presence of antagonists for the previously characterized 5-HT(1A) and 5-HT₂ receptors, a proportion of layer V pyramidal neurons continue to show 5-HT-elicited...

Resistance to virus infections in higher vertebrates is mediated in part through catalysis of RNA decay by the, interferon-regulated 2-5A system. A functional 2-5A system requires two enzymes, a 2-5A synthetase that produces 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) in response to double-stranded RNA, and the 2-5A-dependent RNase L. We have coexpressed these human enzymes in transg...

Previous studies from this laboratory have demonstrated a statistically significant dysregulation in several key components of the 2',5'-oligoadenylate (2-5A) synthetase/RNase L and PKR antiviral pathways in chronic fatigue syndrome (CFS) (Suhadolnik et al. Clin Infect Dis 18, S96-104, 1994; Suhadolnik et al. In Vivo 8, 599-604, 1994). Two methodologies have been developed to further examine th...

The 2-5A system is a recognized mechanistic component of the antiviral action of interferon. Interferon-induced 2-5A synthetase generates 2-5A, which, in turn, activates the latent constitutive RNase L that degrades viral RNA. Chemical conjugation of 2-5A to an antisense oligonucleotide can target the 2-5A-dependent RNase L to the antisense-specified RNA and effect its selective destruction. Su...

Pax6 is essential for development of the eye, olfactory system, brain and pancreas. Haploinsufficiency of Pax6 causes abnormal eye development. Two forms of Pax6 protein, PAX6 and PAX6(5a), differ in a 14 amino acid insertion encoded by an alternatively spliced exon 5a in the N-terminal DNA-binding paired domain (PD), and they are simultaneously expressed. Here, we show that PAX6 and PAX6(5a) t...

A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carot...