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Cancer is a progressive disease culminating in acquisition of metastatic potential by a subset of evolving tumor cells. Generation of an adequate blood supply in tumors by production of new blood vessels, angiogenesis, is a defining element in this process. Although extensively investigated, the precise molecular events underlying tumor development, cancer progression, and angiogenesis remain unclear. Subtraction hybridization identified a genetic element, progression elevated gene-3 ( Taken together these data demonstrate that PEG-3 is a positive regulator of cancer aggressiveness, a process regulated by augmented VEGF production. These studies also support an association between expression of a single nontransforming cancer progression-inducing gene, PEG-3, and the processes of cancer aggressiveness and angiogenesis. In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis.

Varicella-zoster virus (VZV) open reading frame 29 (ORF29) encodes a single-stranded DNA binding protein. During lytic infection, ORF29pis localized primarily to infected-cell nuclei, whereas during latency it appears in the cytoplasm of infected neurons. Following reactivation, ORF29p accumulates in the nucleus. In this report, we analyze the cellular localization patterns of ORF29p during VZV infection and during autonomous expression. Our results demonstrate that ORF29p is excluded from the nucleus in a cell-type-specific manner and that its cellular localization pattern may be altered by subsequent expression of VZV ORF61p or herpes simplex virus type 1 ICP0. In these cases, ORF61p and ICP0 induce nuclear accumulation of ORF29p in cell lines where it normally remains cytoplasmic. One cellular system utilized by ICP0 to influence protein abundance is the proteasome degradation pathway. Inhibition of the 26S proteasome, but not heat shock treatment, resulted in accumulation of ORF29p in the nucleus, similar to the effect of ICP0 expression. Immunofluorescence microscopy and pulse-chase experiments reveal that stabilization of ORF29p correlates with its nuclear accumulation and is dependent on a functional nuclear localization signal. ORF29p nuclear translocation in cultured enteric neurons and cells derived from an astrocytoma is reversible, as the protein's distribution and stability revert to the previous states when the proteasomal activity is restored. Thus, stabilization of ORF29p leads to its nuclear accumulation. Although proteasome inhibition induces ORF29p nuclear accumulation, this is not sufficient to reactivate latent VZV or target the immediate-early protein ORF62p to the nucleus in cultured guinea pig enteric neurons.Chicken pox (varicella) is a manifestation of lytic infection of cutaneous epithelial cells by varicella-zoster virus (VZV), a ubiquitous human alphaherpesvirus. Following lytic infection, VZV establishes latency in the sensory ganglia and can reactivate later during the host's life to cause shingles (zoster), a painful and potentially debilitating disease that may lead to postherpetic neuralgia (1). Recrudescence occurs when cellmediated immunity is decreased, as seen in the elderly and immunocompromised individuals, where it is associated with significant morbidity that may not be relieved by antiviral and analgesic therapy (63). An understanding of the cellular and viral factors that govern VZV latency and reactivation is critical to developing preventive methods and potential therapies for zoster and postherpetic neuralgia.During latency, viral DNA replication, late protein expression, and virion assembly do not occur. It has been reported that transcripts corresponding to the immediate-early and early open reading frames (ORFs) ORF4, -21, -29, -62, -63, and -66 are present in neurons harboring latent VZV (9-13, 15, 25, 36, 50). Proteins expressed by these ORFs are present in the cytoplasm of latently infected neurons (9,12,15,36,49,50). In particular, Lungu et al. demonstrated ...