High impact information on Spn4

• Co-transfection experiments in different mammalian cell lines reveal that in contrast to Sp1 and Sp4, Sp3 is not able to activate several Sp1 responsive promoters [1].
• The Spn4 gene of Drosophila encodes a potent furin-directed secretory pathway serpin [2].
• Neither Sp3 nor Sp4 was able to activate transcription in those cells, and transcriptional activation by Sp1 was repressed by Sp3 or Sp4 [3].
• The zinc-finger domains of Sp3 and Sp4 also bind selectively to the core cis-elements [3].
• However, in contrast to Sp1, Sp4 is not able to act synergistically through adjacent binding sites [4].

Biological context of Spn4

• The Spn4 gene encodes at least two different serpin proteins, generated by alternate splicing of the last coding exon [5].
• The serpin gene Spn4 from Drosophila melanogaster encodes multiple isoforms with alternative reactive site loops (RSL) [6].
• Two secreted forms of neuroserpin were observed with molecular weights of approximately 49 and approximately 50 kDa which may represent alternative glycosylation at three putative N-linked glycosylation sites [7].
• Furthermore, we show that Sp4-mediated transcriptional activation can be repressed by Sp3 [4].
• Sp4 is a human sequence-specific DNA binding protein with structural features similar to those described for the transcription factors Sp1 and Sp3 [4].

Anatomical context of Spn4

• The identification of Spn4A, the most potent and effective natural serpin of PCs identified to date, suggests that Spn4A could be a prototype of endogenous serpins involved in the precise regulation of PC-dependent proteolytic cleavage events in the secretory pathway of eukaryotic cells [2].
• These transcripts may code for eight different Sp4 protein isoforms with different biological functions, which - dependent on the splice pattern - either may be secreted, reside in the endoplasmic reticulum, or may be located in the cytoplasm [8].

Associations of Spn4 with chemical compounds

• The analyses indicate that the Spn4 gene encodes inhibitors that may inhibit serine proteases of the subtilase family (S8), the chymotrypsin family (S1), and the papain-like cysteine protease family (C1), most of them at high rates [9].
• Recombinant neuroserpin was purified by sequential chromatography on Macroprep ceramic hydroxyapatite, Type I, POROS HQ20, Resource Q, and Superdex 75 HR 10/30 media [7].

Analytical, diagnostic and therapeutic context of Spn4

• Here we describe the molecular cloning and functional expression of a novel member of the serpin family, Serine protease inhibitor 4 (Spn4), that we propose is involved in the regulation of peptide maturation in Drosophila [5].
• Immunofluorescence studies show that Spn4A is localized in the endoplasmic reticulum (ER), suggesting that the inhibitor is an interesting tool for investigating the cellular mechanisms regulating furin and for the design of agents controlling prohormone convertases [6].
• Mobility-shift assays performed with the promoter-proximal GC box demonstrated the binding of Sp1, Sp3 and Sp4 to this sequence [10].

References