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Gene Review

NPEPPS  -  aminopeptidase puromycin sensitive

Homo sapiens

Synonyms: AAP-S, Cytosol alanyl aminopeptidase, MP100, PSA, Puromycin-sensitive aminopeptidase
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Disease relevance of NPEPPS

  • Modeling of the pH- and the temperature-dependent deviations of the free to total PSA (prostate specific antigen) ratios for clinical predictability of prostate cancer and benign prostate hyperplasia [1].
  • A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration [2].
  • PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: Results from the European randomized study of screening for prostate cancer, Sweden section [3].
  • Prostate adenocarcinomas with a BRAF mutation tended to show higher preoperative serum PSA levels, Gleason scores and tumor stages than prostate adenocarcinomas with a KRAS mutation [4].
  • Here we have extended these observations using human recombinant PSA purified from Escherichia coli [5].

High impact information on NPEPPS


Chemical compound and disease context of NPEPPS


Biological context of NPEPPS


Anatomical context of NPEPPS

  • Here we report on the analysis of a novel mouse cDNA encoding the puromycin-sensitive aminopeptidase (PSA) and on its expression in COS cells and 3T3 fibroblasts [8].
  • Anti-rat brain-soluble PS-Ap IgG detected immunoreactive material in epithelium, glands, and endothelium [12].
  • In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05) [13].
  • In contrast, since chronic imipramine treatment is not associated with neurogenesis in the medial prefrontal cortex, increased expression of PSA-NCAM and pCREB in the prelimbic cortex implicates changes in synaptic connectivity in this brain region [14].
  • Since PSA-NCAM and pCREB are expressed in recently-generated neurons in the dentate gyrus, it is likely that chronic imipramine treatment increased their expression in the hippocampus at least partially by increasing neurogenesis [14].

Associations of NPEPPS with chemical compounds

  • An analysis of Alzheimer-affected hippocampal and control samples showed that the specific activity (in units per milligram of sodium dodecyl sulfate-soluble protein) of MP-70 varied less than the activities of MP-100 and MP-130 between the two groups [15].
  • One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline [16].
  • Bicalutamide (150 mg) significantly improved time to PSA progression (HR 0.80, 95% CI 0.72 to 0.90, p <0.001) [17].
  • In vivo, candesartan significantly suppressed VEGF expression, serum PSA concentration and tumor growth (1.1 +/- 0.2, 45.0 +/- 17.6 ng/ml, 235.8 +/- 37.4 mm(3)) in C4-2 xenografts in castrated mice, compared with the controls (2.4 +/- 0.6, 376.7 +/- 74.2 ng/ml, 830.8 +/- 147.6 mm(3)) [18].
  • Therefore, SGZ progenitor cells committed to a neuronal phenotype before KA treatment complete their differentiation despite the rapid down-regulation of doublecortin and PSA-NCAM [19].

Other interactions of NPEPPS


Analytical, diagnostic and therapeutic context of NPEPPS


  1. Modeling of the pH- and the temperature-dependent deviations of the free to total PSA (prostate specific antigen) ratios for clinical predictability of prostate cancer and benign prostate hyperplasia. Chen, K.C., Peng, C.H., Wang, H.E., Peng, C.C., Peng, R.Y. Bull. Math. Biol. (2004) [Pubmed]
  2. A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration. Karsten, S.L., Sang, T.K., Gehman, L.T., Chatterjee, S., Liu, J., Lawless, G.M., Sengupta, S., Berry, R.W., Pomakian, J., Oh, H.S., Schulz, C., Hui, K.S., Wiedau-Pazos, M., Vinters, H.V., Binder, L.I., Geschwind, D.H., Jackson, G.R. Neuron (2006) [Pubmed]
  3. PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: Results from the European randomized study of screening for prostate cancer, Sweden section. Ali, K., Gunnar, A., Jan-Erik, D., Hans, L., P??r, L., Jonas, H. Int. J. Cancer (2007) [Pubmed]
  4. BRAF and KRAS mutations in prostatic adenocarcinoma. Cho, N.Y., Choi, M., Kim, B.H., Cho, Y.M., Moon, K.C., Kang, G.H. Int. J. Cancer (2006) [Pubmed]
  5. Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro. Sengupta, S., Horowitz, P.M., Karsten, S.L., Jackson, G.R., Geschwind, D.H., Fu, Y., Berry, R.W., Binder, L.I. Biochemistry (2006) [Pubmed]
  6. The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases. Lévy, F., Burri, L., Morel, S., Peitrequin, A.L., Lévy, N., Bachi, A., Hellman, U., Van den Eynde, B.J., Servis, C. J. Immunol. (2002) [Pubmed]
  7. Major histocompatibility complex class I-presented antigenic peptides are degraded in cytosolic extracts primarily by thimet oligopeptidase. Saric, T., Beninga, J., Graef, C.I., Akopian, T.N., Rock, K.L., Goldberg, A.L. J. Biol. Chem. (2001) [Pubmed]
  8. Puromycin-sensitive aminopeptidase. Sequence analysis, expression, and functional characterization. Constam, D.B., Tobler, A.R., Rensing-Ehl, A., Kemler, I., Hersh, L.B., Fontana, A. J. Biol. Chem. (1995) [Pubmed]
  9. Prednisone monotherapy in asymptomatic hormone refractory prostate cancer. Heng, D.Y., Chi, K.N. The Canadian journal of urology (2006) [Pubmed]
  10. Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase. Thompson, M.W., Tobler, A., Fontana, A., Hersh, L.B. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  11. Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence for a polymorphism at a.a. 140 and refined chromosomal localization to 17q21. Bauer, W.O., Nanda, I., Beck, G., Schmid, M., Jakob, F. Cytogenet. Cell Genet. (2001) [Pubmed]
  12. Aminopeptidase activity in human nasal mucosa. Ohkubo, K., Baraniuk, J.N., Hohman, R., Merida, M., Hersh, L.B., Kaliner, M.A. J. Allergy Clin. Immunol. (1998) [Pubmed]
  13. Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence. Cohen, B.L., Gomez, P., Omori, Y., Duncan, R.C., Civantos, F., Soloway, M.S., Lokeshwar, V.B., Lokeshwar, B.L. Int. J. Cancer (2006) [Pubmed]
  14. Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat. Sairanen, M., O'leary, O.F., Knuuttila, J.E., Castr??n, E. Neuroscience (2007) [Pubmed]
  15. Characterization of neutral proteinases from Alzheimer-affected and control brain specimens: identification of calcium-dependent metalloproteinases from the hippocampus. Backstrom, J.R., Miller, C.A., Tökés, Z.A. J. Neurochem. (1992) [Pubmed]
  16. A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer. Collins, R., Trowman, R., Norman, G., Light, K., Birtle, A., Fenwick, E., Palmer, S., Riemsma, R. Br. J. Cancer (2006) [Pubmed]
  17. The bicalutamide 150 mg early prostate cancer program: findings of the north american trial at 7.7-year median followup. McLeod, D.G., See, W.A., Klimberg, I., Gleason, D., Chodak, G., Montie, J., Bernstein, G., Morris, C., Armstrong, J. J. Urol. (2006) [Pubmed]
  18. Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer. Kosaka, T., Miyajima, A., Takayama, E., Kikuchi, E., Nakashima, J., Ohigashi, T., Asano, T., Sakamoto, M., Okita, H., Murai, M., Hayakawa, M. Prostate (2007) [Pubmed]
  19. Impairment of dentate gyrus neuronal progenitor cell differentiation in a mouse model of temporal lobe epilepsy. Ledergerber, D., Fritschy, J.M., Kralic, J.E. Exp. Neurol. (2006) [Pubmed]
  20. Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma. Varona, A., Blanco, L., López, J.I., Gil, J., Agirregoitia, E., Irazusta, J., Larrinaga, G. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  21. Separation of the 100-kDa membrane protein mediating ADP-induced platelet shape change and activation from glycoprotein IIIa. Colman, R.W., Figures, W.R., Wu, Q.X., Chung, S.Y., Morinelli, T.A., Tuszynski, G.P., Colman, R.F., Niewiarowski, S. Trans. Assoc. Am. Physicians (1986) [Pubmed]
  22. Proteolytic cleavage of the puromycin-sensitive aminopeptidase generates a substrate binding domain. Ma, Z., Daquin, A., Yao, J., Rodgers, D., Thompson, M.W., Hersh, L.B. Arch. Biochem. Biophys. (2003) [Pubmed]
  23. Identification of differentially expressed genes in human pineal parenchymal tumors by microarray analysis. Champier, J., Jouvet, A., Rey, C., Brun, V., Bernard, A., Fèvre-Montange, M. Acta Neuropathol. (2005) [Pubmed]
  24. Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Iran. Safarinejad, M.R. Ann. Oncol. (2006) [Pubmed]
  25. Changes in puromycin-sensitive aminopeptidases in postmortem schizophrenic brain regions. Hui, M., Budai, E.D., Lajtha, A., Palkovits, M., Hui, K.S. Neurochem. Int. (1995) [Pubmed]
  26. In vivo imaging of prostate cancer involving bone in a mouse model. Kundra, V., Ng, C.S., Ma, J., Bankson, J.A., Price, R.E., Cody, D.D., Do, K.A., Han, L., Navone, N.M. Prostate (2007) [Pubmed]
  27. PSA: A Biomarker for Disease. A Biomarker for Clinical Trials. How Useful Is It? Thompson, I.M. J. Nutr. (2006) [Pubmed]
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