Disease relevance of PSMA5

• Our animal study showed that the expression of H2Kd/scPSMA in B16F0/PSMA5, a B16F0 cell line expressing human PSMA, significantly inhibited tumor growth as demonstrated in the pulmonary metastasis assay and tumor growth study and improved overall survival [1].
• Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome [2].
• We confirmed (Petit F et al.: Biochem. J. 326: 93-98 (1997)) that both 20 S proteasomes and free zeta subunits possess RNase activity though the activities were very low: 4 mMoles and 0.6 mMoles of tobacco mosaic virus RNA degraded per mole of enzyme per min, respectively [3].
• To better characterize human alpha5-subunit (PSMA5) of the 20S proteasome, we have established a high-efficiency Escherichia coli expression system [4].
• A human immunodeficiency virus (HIV) envelope-specific UR consisting of the extracellular domain of human CD4 linked to the zeta chain of the T cell receptor (CD4 zeta) was introduced ex vivo into murine HSC by retroviral transduction [5].

Psychiatry related information on PSMA5

• Alzheimer's disease associated presenilin 1 interacts with HC5 and ZETA, subunits of the catalytic 20S proteasome [6].
• CJD patients showed five dominant 14-3-3 isoforms, gamma, epsilon, zeta, eta and beta, but 14-3-3 tau, which mainly originates from T lymphocytes, was not detected [7].
• The human alpha-like globins undergo a switch from the embryonic zeta-chain to the alpha-chain early in human development, at approximately the same time as the beta-like globins switch from the embryonic epsilon-to the fetal gamma-chains [8].
• An examination of the specific PKC isozymes in cortical homogenates revealed that cytosolic alpha- and membrane-associated gamma- and zeta PKC isozymes were elevated in cortices of bipolar affective disorder subjects, whereas cytosolic epsilon PKC was found to be reduced [9].
• The nanocomposite particles were characterized by transmission electron spectroscopy, X-ray diffraction (XRD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), BET N(2) gas adsorption, sedimentation time studies, acid dissolution, and zeta potential (zeta) [10].

High impact information on PSMA5

• The zeta 2-containing receptors are fully capable of transducing signals leading to IL-2 production and growth inhibition, while the presence of the zeta eta heterodimer is associated with the autolytic response of T-cell hybridomas to activation [11].
• The zeta eta heterodimer appears to be largely responsible for coupling receptor occupancy to PI hydrolysis, the zeta 2 heterodimer may couple to tyrosine kinase activation and/or other signaling pathways [11].
• We have recently identified a 70 kd tyrosine phosphoprotein (ZAP-70) that associates with zeta and undergoes tyrosine phosphorylation following TCR stimulation [12].
• The compact size of the motif appears to eliminate zeta mechanisms based on enzymatic activity and suggests that one or at most a few cellular proteins interact with the zeta intracellular domain to initiate signal transduction [13].
• We have reduced the active site of zeta to an 18 residue motif that can be appended to the intracellular domain of other transmembrane proteins to endow them with receptor-like activity [13].

Chemical compound and disease context of PSMA5

• Here, we propose that in lupus lymphocytes, the receptor-mediated increase in protein tyrosine phosphorylation and cytoplasmic free Ca2+ responses, along with T-cell receptor zeta chain deficiency, might explain the previously described diverse and conflicting immunoregulatory defects in human lupus [14].
• The development of gallstones depends in part on biliary cholesterol saturation and on the zeta potential of bile [15].
• These results suggest that the increased incidence of cholelithiasis following small bowel bypass is not only due to a relative change in bile composition but is probably more significantly due to an increase in the biliary glycine/taurine ratio and a consequent decrease in the biliary zeta potential [15].
• Furthermore, using proteins expressed in Escherichia coli, a glutathione S-transferase-Nef fusion protein coprecipitated histidine-tagged portions of the TCR zeta cytoplasmic domain which contained SNID-1 or SNID-2 [16].
• Concomitantly the backbone torsion angles of the pyrimidine moieties have larger gamma values, larger epsilon values, and smaller zeta values than the purines [17].

Biological context of PSMA5

• The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways [18].
• The other is a pseudogene (psi zeta) that differs by only 3 bp in the protein coding sequence, one of which converts the codon for amino acid 6 into a chain termination codon [19].
• Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the alpha-globin locus on the short arm of chromosome 16 (zeta = 25.85, theta = 0.05) [20].
• This action is combined with that of DNA polymerase Pol zeta, which is essential for damage-induced mutagenesis, to complete the lesion bypass [21].
• The Src homology region 2 (SH2) domain of Shc directly interacted with the tyrosine-phosphorylated zeta chain of the TCR [22].

Anatomical context of PSMA5

• One of them, zeta, was found in HeLa cells at a concentration of 890 microg per g of cell protein [3].
• Purification and refolding of human alpha5-subunit (PSMA5) of the 20S proteasome, expressed as inclusion bodies in Escherichia coli [4].
• CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex [23].
• Furthermore, zeta- and beta-globin synthesis is restricted to primitive and definitive erythroblasts respectively [24].
• Following termination of the pregnancy, the diagnosis was established by the presence of only hemoglobins Barts (gamma 4) and Portland (zeta 2 gamma 2) in the fetal blood [25].

Associations of PSMA5 with chemical compounds

• Recent studies suggest that zeta has a critical role in allowing antigen to activate the cell, whereas eta expression has been correlated with the capacity for antigen-induced phosphoinositide turnover [26].
• Furthermore, nuclear Overhauser effects (NOEs) were observed between the zeta 3 and epsilon 3 protons of the methylleucine (MeLeu) residue at position 9 of CsA and tryptophan121 (Trp121) and phenylalanine (Phe) protons of cyclophilin, suggesting that the MeLeu9 residue of CsA interacts with cyclophilin [27].
• Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta [28].
• Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced zeta chain degradation, leading to the accumulation of zeta chain in large Lamp1(+) vesicles [29].
• RESULTS: Treatment with indomethacin decreased the abundance of PKC-beta1 and increased that of PKC-beta2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and micro [30].

Other interactions of PSMA5

• Furthermore, we were able to coimmunoprecipitate the transfected binding partners, as well as the endogenous PSEN1 and ZETA proteins from HEK 293T cells [6].

Analytical, diagnostic and therapeutic context of PSMA5

• To produce the native PSMA5, straightforward protocols have been developed for refolding the human PSMA5 in the presence of surfactants using dilution refolding and size-exclusion chromatography matrix refolding methods [4].
• Dissection of the TCR utilizing chimeric receptors and TCR mutants has demonstrated that the multi-subunit receptor is composed of at least two signal transducing modules, the CD3 and the zeta chain subunits [31].
• T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-beta, CD3-epsilon, and zeta chains, as detected by FACS(R) analysis on fixed and permeabilized T-APC conjugates and by Western blot analysis on cell lysates [29].
• Here we show that ligation of T cell receptor (TCR) by alloantigen alone, which results in anergy, activates tyrosine phosphorylation of TCR zeta and its association with fyn [32].
• Our findings demonstrate both functional and physical association of p56lck with Fc gamma RIIIA, through direct interaction of the kinase with the zeta and/or the gamma signal transducer subunits of the receptor [33].

References