Disease relevance of MYCBP2

• METHODS: We compared the antibody response to immunization with two conjugates, Tn(c)-keyhole limpet hemocyanin (KLH) and Tn(c)-palmitic acid (PAM) with the saponin immunologic adjuvant QS21, in a phase I clinical trial in patients with biochemically relapsed prostate cancer [1].
• PAM, a novel plasminogen-binding protein from Streptococcus pyogenes [2].
• After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LüH6)] were compared in clinical trials [3].
• A medium (PAM: Providencia alcalifaciens medium) is described that enables the presence of the enteropathogen P. alcalifaciens in faeces to be detected with ease and simplicity [4].
• The cisplatin-resistant murine leukemia L1210 cell line L1210/PAM has an elevated cellular glutathione content, as compared to its sensitive parent cell line, L1210/*. Exposure to D,L-buthionine-S,R-sulfoximine reduced L1210/PAM cells' glutathione content to nearly that of L1210/* cells and abrogated the resistance to cisplatin [5].

Psychiatry related information on MYCBP2

• The average psychometric curve revealed that the threshold for PAM detection was 314 degrees /s. The minimum and maximum thresholds for individual subjects were 277 degrees and 378 degrees /s, respectively [6].
• At posttreatment, results indicated that within the child-anxiety-only condition, 82% of the children in the CBT condition no longer met criteria for an anxiety disorder compared with 80% in the CBT + PAM condition [7].

High impact information on MYCBP2

• Here we show that PAM is localized at the endoplasmic reticulum in HeLa cells and that upon serum treatment PAM is recruited to the plasma membrane, causing an inhibition of adenylyl cyclase activity [8].
• Within 15 min after incubation with S1P, PAM appeared at the plasma membrane and was detectable for up to 120 min [8].
• We purified the serum factor that induced PAM translocation and identified it as sphingosine-1-phosphate (S1P) [8].
• In the late phase, adenylyl cyclase inhibition was PAM dependent and attenuated cyclic AMP (cAMP) signaling by various cAMP-elevating signals [8].
• PAM is located within a 300-kb region on chromosome 13q22 [9].

Chemical compound and disease context of MYCBP2

• Seventy-six evaluable patients with ovarian carcinoma stages FIGO IIb, IIc, III, and IV, either received cis-platin (P) (80 mg/m2 iv. day 1), melphalan (PAM) (12 mg/m2 i.v. day 2) and hexamethylmelamine (HEXAPAMP) (135 mg/m2 orally days 8 to 21) or the same dose of cis-platin and melphalan but no hexamethylmelamine (PAMP) every four weeks [10].

Biological context of MYCBP2

• A radiolabeled proteolytic plasminogen fragment containing the first three kringles (K1-K3) interacted with streptococci expressing PAM or a chimeric surface protein harboring the a1a2 sequence [11].
• The DNA sequence data also proved the relationship of the encoded protein, named PAM, to the M proteins [2].
• Here, we describe the relationship between plasminogen-binding capacity of GAS isolates, PAM genotype, and invasive capacity in 29 GAS isolates belonging to 25 distinct strains from the NT [12].
• Despite considerable amino acid sequence variation within the A1 repeat region of PAM where the plasminogen-binding domain maps, the critical lysine residue was conserved [12].
• RESULTS: We apply our analysis to the comparative study of amino acid substitution matrix families and find that using modern matrices results in a small, but statistically significant improvement in remote homology detection compared with the classic PAM and BLOSUM matrices [13].

Anatomical context of MYCBP2

• The gene encoding Pam (PAM) is expressed in all of the human tissue examined, but expression is exceptionally abundant in brain and thymus [9].
• Coexpression of ACV and full-length PAM or its N-terminal third (PAM-N) in COS-7 cells inhibited isoproterenol-stimulated cAMP accumulation [14].
• Here, we demonstrate that PAM mRNA is highly expressed in specific anatomical regions including hippocampus, dentate gyrus and cerebellum [15].
• In these areas, PAM mRNA is restricted to pyramidal cells of hippocampus and granule cells of dentate gyrus and cerebellum [15].
• These results demonstrate for the first time a bidirectional activating interaction between iDCs and PAM-stimulated gammadelta T lymphocytes, thus suggesting a potential adjuvant role of this early cross-talk in the therapeutic activity of aminobiphosphonate drugs [16].

Associations of MYCBP2 with chemical compounds

• PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate [8].
• We reported previously that protein associated with Myc (PAM) interacts with the C2 domain of type V adenylyl cyclase (ACV-C2) and that purified PAM is a potent inhibitor of Galphas-stimulated ACV activity (J Biol Chem 276:47583-47589, 2001) [14].
• Collateral sensitivity of the G3361/CP, G3361/PAM, and G3361/4HC lines to killing by BCNU was also observed [17].
• The insertion of an alanine between Pro-1 and Met-2 (PAM) abolishes a non-physiological catalytic activity, and this mutant is defective in the in vitro glucocorticoid counter-regulatory activity of MIF [18].
• In contrast, plasminogen fragments containing kringle 4 or kringle 5 and the activable serine proteinase domain failed to bind to PAM-expressing group A streptococci [11].

Other interactions of MYCBP2

• Developmental expression of PAM (protein associated with MYC) in the rodent brain [15].

Analytical, diagnostic and therapeutic context of MYCBP2

• Expression patterns of PAM in both rat and mouse brains were examined by using in situ hybridization [15].
• Using the yeast two-hybrid assay and the second of the two large cytosolic domains of type V adenylyl cyclase (ACV) as bait, we identified a small region (amino acids 1028-1231) in the protein associated with Myc (PAM) as an interaction site for ACV [19].
• Two-dimensional gel electrophoresis identified 13 different proteins migrating at 60 kDa; 5 were splice variants of HSP60, and 2 corresponded with a protein associated with MYC (PAM) [20].
• Expression of a plasminogen-binding GAS M-like protein (PAM) has been associated with skin infection in isolates elsewhere (D. Bessen, C. M. Sotir, T. M. Readdy, and S. K. Hollingshead, J. Infect. Dis. 173:896-900, 1996), and subversion of the host plasminogen system by GAS is thought to contribute to invasion in animal models [12].
• In order to assess the potential phytotoxic impact of herbicide residues in the estuaries, surface waters were analysed with a PAM fluorometry-based bioassay that employs the photosynthetic efficiency (photosystem II quantum yield) of laboratory cultured microalgae, as an endpoint measure of phytotoxicity [21].

References