Disease relevance of PRIM1

• Amplifications of DNA primase 1 (PRIM1) in human osteosarcoma [1].
• These results were in accordance with the specific presence of p49 in primary radiation-induced myeloid leukemia and its absence in spontaneous B lymphoma [2].
• In contrast, global translation arrest was observed in cells infected with AcMNPV in which p35 was replaced with Opiap, Cpiap, or p49, baculovirus apoptotic suppressors that block apoptosis by different mechanisms than p35 [3].
• Interestingly, p49/p100 as well as p105 maps to regions associated with certain types of acute lymphoblastic leukemia [4].
• These peptides were derived from the amino acid sequences of the two major viral capsid proteins of HPV 16, p(31) L1 and (p49) L2 [5].

High impact information on PRIM1

• As indicated by the addition of specific antibodies to cytolytic tests, all the above receptors contributed to HLA-G1 recognition by decidual NK cells, although p49 would appear to play a predominant role [6].
• Transactivation mediated by the p49/p100 and p65 NF-kappa B proteins is therefore sensitive to minor changes in the sequence of the kappa B site [7].
• These properties imply that p49 might be involved in the regulation of hematopoietic cell growth or differentiation [2].
• However, its detection in the bone marrow by the B92 antibody seemed to stem from the abundance of p49 in immature cells of the myeloid lineage [2].
• Furthermore, our results suggest that a Re1NA-like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c-Re1 during T-cell activation [8].

Biological context of PRIM1

• Assignment of the 49-kDa (PRIM1) and 58-kDa (PRIM2A and PRIM2B) subunit genes of the human DNA primase to chromosome bands 1q44 and 6p11.1-p12 [9].
• DNA primase, consisting of two subunits (p49 and p58), plays a key role in both the initiation of DNA replication and the synthesis of Okazaki fragments for lagging strand synthesis [9].
• We studied the involvement of PRIM1 in osteosarcoma by differential display, Northern and Southern hybridization, as well as fluorescence in situ hybridization (FISH) on interphase nuclei [1].
• FVIIa evoked a dose-dependent increase in cell proliferation and PRIM1 induction, which were markedly potentiated (4-5-fold) by the presence of TF and abrogated by TF antisense oligonucleotide [10].
• Because DNA primase 1 (PRIM1) plays an essential role in cell proliferation, we used the cloned PRIM1 promoter upstream of the reporter gene chloramphenicol acetyl transferase (CAT) to elucidate the mode of action of FVIIa [10].

Anatomical context of PRIM1

• The p49 receptor, unlike the other KIR, appears to be selectively expressed by decidual NK cells [11].
• Thus the signaling pathway leading to inhibitory tyrosine phosphorylation of p34cdc2 and G2-arrest in irradiated human leukemic B-cell precursors functions independent of p49 WEE1 HU and enzymes which augment the tyrosine kinase activity of p49 WEE 1HU [12].
• In addition, oNADPH markedly inhibited the affinity labeling of p49-phox with [32P]oGTP and [32P]oATP, well reflecting its inhibitory effect on the oxidase activity in the cell-free system, which was previously reported to propose the NADPH-binding site in a cytosolic component [13].

Associations of PRIM1 with chemical compounds

• To further explore these homologies as well as provide insights into the mechanism of primase, we generated three mutants (R304K, R304Q, and R304A) of the p49 subunit at an arginine that is highly conserved between primase and the eukaryotic family X polymerases [14].
• Deleting M288-L313 of the p58 subunit results in a protein that binds to the primase p49 subunit but cannot support primer synthesis on any template when assays only contain Mg(2+) as the divalent metal [15].
• The effects of Mn(2+) involve multiple metal binding sites on primase and may involve both the catalytic p49 subunit as well as the p58 subunit [16].
• In contrast, FK506 or EGTA (Ca2+ chelator) similarly affected the formation of kappa B-like site binding complexes, which were not recognized by any antibodies against the human Rel family proteins (c-Rel, p65, p50, and p49) [17].
• A new TaqI BO variant detected with the p49 probe on the human Y chromosome [18].

Other interactions of PRIM1

• With the use of DNA polymerase beta (pol beta) as a paradigm for family X polymerases, these homologies include both the catalytic core domain/subunit of each enzyme (31 kDa domain of pol beta and p49 subunit of primase) as well as the accessory domain/subunit (8 kDa domain of pol beta and p58 subunit of primase) [14].

Analytical, diagnostic and therapeutic context of PRIM1

• The PRIM1 gene was mapped to 1q44, and two PRIM2 loci (PRIM2A and PRIM2B) were detected at 6p11.1-p12 by fluorescence in situ hybridization using several genomic DNA probes [9].
• Nuclear localization of p49 was further demonstrated by subcellular fractionation followed by Western blotting [2].
• One year after BMT 1/4 of the autologous and 2/3 of the allogeneic BMT patients who were IgG positive to p49 (L2) lost these antibodies as measured by the peptide ELISA assay [5].
• The CPB was performed with a silicone coated oxygenator, Mera Excelung Binding Prim HPO 15 H-C (Group I, n = 6) or Binding Prim HPO 25 H-C (Group II, n = 10) (Senko Medical Instrument Mfg., Tokyo, Japan) [19].

References