Disease relevance of PRIMA1

• Expression proteomics to p53 mutation reactivation with PRIMA-1 in breast cancer cells [1].
• Comparison of TechLab Clostridium difficile Tox-A enzyme immunoassay and Bartels Prima system toxin-A EIA [2].
• METHODS: Forty patients with aortic stenoses, over the age of 75 years, were randomized to receive either the stented Perimount (n=20) or the stentless Prima Plus (n=20) bioprosthesis [3].
• The effects of PRIMA-1 on wild-type (WT) mouse leukemia L1210 cells and drug-resistant L1210 cells (Y8) were studied with respect to the induction of apoptosis and necrosis in these cell lines [4].

High impact information on PRIMA1

• Furthermore, we demonstrate that AChE is actually anchored in neural cell membranes through its interaction with PRiMA [5].
• Finally, we propose that only PRiMA anchors AChE in mammalian brain and muscle cell membranes [5].
• Functional localization of acetylcholinesterase (AChE) in vertebrate muscle and brain depends on interaction of the tryptophan amphiphilic tetramerization (WAT) sequence, at the C-terminus of its major splice variant (T), with a proline-rich attachment domain (PRAD), of the anchoring proteins, collagenous (ColQ) and proline-rich membrane anchor [6].
• Interestingly, short PRiMA mutants, truncated within the proline-rich motif, reduced both cellular and secreted AChE activity, suggesting that their interaction with AChE(T) subunits induces their intracellular degradation [7].
• Expression of AChE(T) subunits in transfected COS cells with a truncated PRiMA, without its transmembrane and cytoplasmic domains (P(stp54) mutant), produced secreted heteromeric complexes (T(4)-P(stp54)), instead of membrane-bound tetramers [7].

Chemical compound and disease context of PRIMA1

• The effect of combined treatment of PRIMA-1 and adriamycin in breast cancer cells was determined with a cytotoxicity assay in vitro [8].

Biological context of PRIMA1

• In brain and muscles, the hydrolysis of acetylcholine by cholinesterases, in different contexts, and their possible noncatalytic functions clearly depend on their localization by ColQ or PRiMA [9].
• These molecules are hetero-oligomers, composed of four AChE catalytic subunits of type T (AChE(T)), associated with a transmembrane protein of type 1, called PRiMA (proline-rich membrane anchor) [7].
• In this study, we used a series of deletions and point mutations to analyze the interaction between the extracellular domain of PRiMA and AChE(T) subunits [7].
• To identify molecular targets that are involved in PRIMA-1-induced apoptosis, we used a proteomics approach with two-dimensional gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry for protein identification [1].
• However, Fas, Bcl-2 family proteins, and caspases were not involved in PRIMA-1-induced cell death [10].

Anatomical context of PRIMA1

• PRIMA-1 inhibited the growth of cell lines derived from various human tumor types in a mutant p53-dependent manner [11].
• Here we report the statistical analysis of the effect of PRIMA-1 on a panel of human tumor cell lines using information available in a database at the Developmental Therapeutics Program of the National Cancer Institute (NCI) [11].
• We have implanted stentless aortic valves (Prima valve) in 31 patients [12].
• From November 1992 to October 1993 we randomized 101 patients over 60 years of age undergoing elective aortic valve replacement, with or without concomitant coronary artery bypass grafting, to receive either a cryopreserved aortic or pulmonary homograft (n = 38) or a stentless porcine aortic valve xenograft (Edwards Prima 2500) (n = 63) [13].
• Between January 10, 1994 and January 4, 1996 nine adult patients (age 31-51 years) underwent aortic valve replacement with an autologous pulmonary valve and right ventricular outflow tract reconstruction with the Edwards Prima or Medtronic Freestyle xenograft [14].

Associations of PRIMA1 with chemical compounds

• We confirmed the importance of the polyproline stretches and defined a peptidic motif (RP(4)LP(10)RL), which induces the assembly and secretion of a heteromeric complex with four AChE(T) subunits, nearly as efficiently as the entire extracellular domain of PRiMA [7].
• PRiMA consists of a signal peptide, an extracellular domain that contains a proline-rich motif (14 prolines with an intervening leucine, P(4)LP(10)), a transmembrane domain, and a cytoplasmic domain [7].
• Serum specimens from 246 women of childbearing age were tested for immunoglobulin G (IgG) antibodies to Toxoplasma gondii by four different commercial assays: Abbott IMx microparticle enzyme immunoassay (EIA), Mercia Toxo-G EIA, Bartels Prima EIA, and bioMerieux Vitek (VIDAS) enzyme-linked fluorescent assay [15].
• Progestin-dependent VEGF induction was completely inhibited by PRIMA-1-activated p53 in all cell-types, but progestin-dependent transcription of a progesterone-regulated minimal promoter was only partially inhibited [16].
• Flavopiridol in combination with PRIMA-1 caused a synergistic increase in necrosis in the WT L1210 cells while LY 294002 in combination with PRIMA-1 caused a synergistic increase in apoptosis in the Y8 L1210 cells [4].

Regulatory relationships of PRIMA1

• PRIMA-1 induced p53 protein in the HCC-1428 cells while levels of mutant p53 protein in T47-D and BT-474 remained unaltered [16].

Other interactions of PRIMA1

• In a similar assay PRIMA1 does not have any effect on p53 core DNA-binding activity [17].
• The tetrameric globular (G4) form of AChE is characterized by linkage to PRiMA [18].
• PRIMA-1 treatment also resulted in the translocation of Hsp90alpha to the nucleus by 8 hours [8].
• By using PCR cloning and sequencing approaches, we obtained genomic sequences of Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin) from the cvs Prima and Fiesta, the two parents of a European reference mapping population [19].

Analytical, diagnostic and therapeutic context of PRIMA1

• CONCLUSIONS: This study suggests that the Prima valve is a reliable stentless aortic bioprosthesis [20].
• The PCR genomic cloning and sequencing were performed on two cultivars, Prima and Fiesta, which resulted in 37 different Mal d 1 gDNA sequences [21].
• Eleven types of stentless xenograft valves were implanted: Medtronic Freestyle in 221 patients (55%), Shelhigh in 55 (14%), Shelhigh composite conduit in 33 (8%), Sorin in 26 (6%), Cryolife O'Brien in 25 (6%), Aortech-Elan in 17 (4%), Edwards Prima in 14 (4%), Toronto SPV in 7 (2%), and other valves in 6 (1%) [22].
• In response to these challenges novel devices are being developed: (1) for restenosis, intracoronary radiation therapy (brachytherapy); (2) for chronic total occlusions, Prima Laser wire; (3) for diffuse small-vessel disease, percutaneous myocardial laser revascularization; and (4) for aged vein grafts, antiembolization devices [23].
• METHODS: Thirty-five patients (age, 77 +/- 6 years; 19 men) were prospectively studied by Doppler echocardiography at 1 month and 52 +/- 8 months after implantation of a Prima stentless valve [20].

References