Disease relevance of Rev3l

• The c-Abl NES can functionally complement an NES-defective HIV Rev protein (RevDelta3NI) and can mediate the nuclear export of glutathione-S-transferase [1].
• Recombinant retroviral vectors that express the Env and Rev proteins of feline immunodeficiency virus (FIV) were prepared and analyzed in a mouse model system for their ability to induce antigen-specific CD8+ CTL (cytotoxic T lymphocyte) responses [2].
• Horizontal transmission in sheep and delayed clearance in guinea pigs and mice of a Brucella melitensis Rev. I mutant [3].

High impact information on Rev3l

• Mutations can be introduced by error-prone polymerases such as polymerase zeta (Rev3), a mispair extender, and polymerase eta, a mispair inserter with a preference for dA/dT, while repairing DNA lesions initiated by AID-mediated deamination of dC to yield dU:dG mismatches [4].
• Rev3(-/-) cell lines could not be established, indicating a cell-autonomous requirement of Rev3 for long-term viability [5].
• The Rev3 gene of Saccharomyces cerevisiae encodes the catalytic subunit of DNA polymerase zeta that is implicated in mutagenic translesion synthesis of damaged DNA [5].
• Histochemical analysis of Rev3(-/-) embryos did not reveal aberrant replication or cellular proliferation but demonstrated massive apoptosis in all embryonic lineages [5].
• The inner cell mass of cultured Rev3(-/-) blastocysts dies of a delayed apoptotic response after exposure to a low dose of N-acetoxy-2-acetylaminofluorene [5].

Chemical compound and disease context of Rev3l

• Binding studies using an eight-residue NPF-containing peptide derived from RAB, the cellular cofactor of the HIV Rev protein, show a hydrophobic peptide-binding pocket formed by conserved tryptophan and leucine residues [6].

Biological context of Rev3l

• Molecular cloning, expression and chromosomal localisation of the mouse Rev3l gene, encoding the catalytic subunit of polymerase zeta [7].
• Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage [5].
• A significant increase in double-stranded DNA breaks as well as chromatid and chromosome aberrations was observed in cells from Rev3(-/-) embryos [5].
• Although increased levels of p53 are detected in Rev3(-/-) embryos, the embryonic phenotype was not rescued by the absence of p53 [5].
• We show that Rev3(-/-) blastocysts were unable to survive and grow in culture but expression of a Rev3 transgene restored their outgrowth [8].

Anatomical context of Rev3l

• Fibroblasts could not be derived from the Rev3l(-/-) embryos, and Rev3l(-/-) embryonic stem (ES) cells could not be obtained [9].
• Rev3l expression, traced by beta-galactosidase staining, was first detected during early somitogenesis and gradually expanded to other tissues of mesodermal origin, including extraembryonic membranes [10].
• In Rev3l(-/-) embryos, no haematopoietic cells other than erythrocytes could be identified in the yolk sac [9].
• Northern blot analysis of various tissues of the mouse revealed that transcription of the Rev3l gene was highest in brain, ovaries and testis [7].
• To investigate the function of its mouse homologue, we have generated mouse embryonic stem cells and mice carrying a targeted disruption of Rev3 [5].

Associations of Rev3l with chemical compounds

• In addition, Rev peptide could potentiate the doxorubicin-induced decrease of cellular viability in U1 bladder cancer cells and inhibition of tumor growth in nude mice [11].
• Immortalized mouse cell lines that lack a functional Rev3 gene are hypersensitive to UV irradiation and cisplatin treatment [12].
• A cDNA that when expressed has the binding and functional characteristics of the pharmacologically defined EP2 prostaglandin (PG) receptor [Cardiovasc. Drug Rev. 11:165-179 (1993)] has been cloned from a human placenta library [13].

Physical interactions of Rev3l

• The Rev peptide that binds to nucleophosmin/B23 with the highest affinity exhibited the greatest cytotoxicity on Ras-3T3 cells and inhibited tumor growth most effectively in nude mice [11].

Other interactions of Rev3l

• Analyses of a REV1 deletion mutant also revealed a significant reduction in recombination-independent ICL repair, suggesting that Rev1 cooperates with Rev3 in recombination-independent ICL repair [14].
• These results reveal an essential role for REV3 in the survival and growth of mammalian cells and suggest that Rev3(-/-) embryonic death occurs in a p53-independent pathway [8].

Analytical, diagnostic and therapeutic context of Rev3l

• Hence, stable transduction of CD4+ T cells with Rev M10 represents a novel gene therapy aimed at inhibiting HIV replication within these cells, thereby slowing the progression of AIDS [15].

References