Disease relevance of PSAP

• These findings suggest that the PSAP motif of M protein is not critical for budding and that there are fundamental differences between PTAP-containing viruses (Ebola virus and human immunodeficiency virus type 1) and PPPY-containing viruses (VSV and rabies virus) regarding their dependence on specific host factors for efficient budding [1].
• The retrovirus Mason-Pfizer monkey virus (MPMV) carries closely spaced PPPY and PSAP motifs [2].
• A cDNA coding for SAP-1 was isolated from a lambda gt11 human hepatoma expression library using polyclonal antibodies raised against human SAP-1 [3].
• Vesicular stomatitis virus (VSV) possesses a PPPY and a PSAP motif within the matrix (M) protein [4].
• Three different critical core sequences have been identified as required elements for L-domain function: PPPY, PTAP (also PSAP), and YPDL, with different retroviruses utilizing one or two of these core sequences [5].

High impact information on PSAP

• The lysosomal removal of the sulfate moiety from sulfatide requires the action of two proteins, arylsulfatase A and sphingolipid activator protein-1 (SAP-1) [6].
• Correction of sulfatide metabolism after transfer of prosaposin cDNA to cultured cells from a patient with SAP-1 deficiency [6].
• We now report the insertion of the full-length prosaposin cDNA into the Moloney murine leukemia virus-derived retroviral vector, pLJ, and the infection of cultured skin fibroblasts from a newly diagnosed and molecularly characterized patient with SAP-1 deficiency [6].
• Further, a PSAP motif-mutated ORF3 protein was unable to associate with TSG101 and also lost its ability to enhance the secretion of alpha1 microglobulin [7].
• In the present study, we discovered that the ability of the ORF3 protein to expedite alpha1 microglobulin secretion is attributed to the PSAP motif present at the C terminus of the former [7].

Biological context of PSAP

• Complete amino-acid sequence of the naturally occurring A2 activator protein for enzymic sphingomyelin degradation: identity to the sulfatide activator protein (SAP-1) [8].
• VSV recombinants with mutations in the PPPY and/or PSAP motif were recovered by reverse genetics and examined for growth kinetics, plaque size, and budding efficiency by electron microscopy [9].
• The nonconstant display of PSAP and PSA showed a moderate tendency to cell differentiation in WAJC 404 medium [10].
• The mitochondrial localization and proapoptotic activity of PSAP suggest that it is an important regulator of apoptosis [11].
• PSAP-induced cell death was accompanied by cytochrome c release from mitochondria and caspase-3 activation [11].

Anatomical context of PSAP

• The cultured cells infected with the prosaposin cDNA construct now show both production of normal levels of mature SAP-1 and completely normal metabolism of endocytosed [14C]-sulfatide [6].
• Two of the major proteins secreted by the prostate epithelium secretory cells are PSA (prostate-specific antigen) and PSAP (prostatic-specific acid phosphatase) [12].

Associations of PSAP with chemical compounds

• Direct assay of the removal of hydrogen peroxide and glutathione from reaction mixtures confirmed the peroxidase-like activities of these selenoorganic compounds, but indicate that the conventional coupled GSSG reductase assay may be unsuitable for the assessment of the catalytic capacity of PSAP and Ebselen [13].
• Fluoxetine significantly improved PSEI and PSAP, whereas no definitive improvement of PSD was found [14].
• Androgen-dependent PSAP secretion was significantly inhibited in cells that expressed the C2A domain of JFC1 [PtdIns(3,4,5)P3-binding-domain], but was unaffected by JFC1 overexpression [12].

Other interactions of PSAP

• The attenuated epithelial lesions of these mutants were correlated not only with reduced expression of the hyphal-associated gene SAP4, but also with the lack of SAP1 and SAP3 expression previously shown to be important for oral infections [15].

Analytical, diagnostic and therapeutic context of PSAP

• Examination of HeLaP4 cells expressing PSAP mutant virus by electron microscopy revealed mostly late budding structures and chains of viruses accumulating at the cell surface with little free virus [2].
• Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator [3].
• Correlation between immunohistochemical patterns and serum levels of PSA and PSAP in prostatic pathology: evaluation of 198 prostatic fine needle biopsies [16].
• Northern blot analysis revealed that PSAP is predominantly expressed in the brain [17].
• PSAP was detected in a mitochondria-enriched fraction, and PSAP immunofluorescence was present in a punctate pattern that colocalized with a mitochondrial marker [11].

References