Disease relevance of EXOSC8

• Using a modified DNA mobility shift assay, we have identified and purified a novel 9-kDa polypeptide (designated p9) from plasmacytoma nuclear extracts which forms salt-stable DNA-protein complexes without apparent sequence specificity [1].
• Osteoclast inhibitory peptide 2 (OIP-2) is a novel autocrine/paracrine factor produced by osteoclasts (OCLs) that inhibits bone resorption and OCL formation in vitro and in vivo [2].
• Analyses of EIAV Gag constructs with progressive N-terminal or C-terminal deletions of the p9 protein identified a minimum sequence of 11 amino acids (Q20N21L22Y23P24D25L26S27E28I29K30) capable of providing the late assembly function [3].
• Taken together, these data demonstrate that the EIAV YPDL L domain mediates distinct functions in viral budding and infectivity and that the HIV-1 PTAP and RSV PPPY L domains can effectively facilitate these dual replication functions in the context of the p9 protein [4].
• Equine infectious anemia virus utilizes a YXXL motif within the late assembly domain of the Gag p9 protein [3].

High impact information on EXOSC8

• A protein subunit of human RNase P, Rpp14, and its interacting partner, OIP2, have 3'-->5' exoribonuclease activity [5].
• On Northern blots, p9 cDNA hybridized with a mRNA species of comparable size from both mouse and human cell lines, suggesting a significant degree of interspecies sequence conservation [1].
• The proform or the CTF portion of OIP-2 inhibited OCL formation in a dose-dependent manner in murine bone marrow cultures stimulated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] [2].
• Alanine scanning studies of this L-domain sequence demonstrated that mutations of residues Y23, P24, and L26 abrogated the p9 late budding function; mutations of other residues in the p9 L domain did not substantially affect the level of EIAV Gag particle assembly [3].
• The results of these particle budding assays revealed that expression of EIAV Gag polyprotein in COS-1 cells yielded extracellular Gag particles with a characteristic density of 1.18 g/ml, while expression of EIAV Gag polyprotein lacking p9 resulted in a severe reduction in the release of extracellular Gag particles [3].

Chemical compound and disease context of EXOSC8

• The p9 protein had a repeating Cys residue containing motif which is found in the nucleic acid-binding Cys residue-containing proteins of retroviruses [6].

Biological context of EXOSC8

• The same preinsertion sequences in the DNA of cell line BHK21 and on the non-occupied chromosome in the tumor cell line H1111(2) in passage 9 (p9) are almost completely methylated [7].

Anatomical context of EXOSC8

• The p9-RNA was also able to activate the RNA-dependent protein kinase (PKR) of human lymphocytes [8].
• Previous results with p9-RNA, obtained from lymph nodes of animals immunized with the peptide p9 of HIV-1, suggested that its effects on lymphocytes could be mediated by RNA-dependent protein kinase (PKR) [9].

Analytical, diagnostic and therapeutic context of EXOSC8

• Amino acid and cDNA sequence analyses demonstrated that p9 derives from the 77-residue C-terminal domain of a 14-kDa polypeptide comprised of 127 amino acids [1].
• Hospitalization due to granulocytopenic fever was required in 15/78 (19%) EAP-1 versus 20/215 (9%) EAP-2 courses [10].
• The fractionation of p9-RNA by affinity chromatography indicates that the poly A(+) p9-RNA is the fraction responsible for PKR activation [9].

References