GPBP

GPBP is a nonconventional protein kinase for the noncollagenous-1 domain (NC1) of the α3 chain of the type IV collagen of the glomerular basement membrane [α3(IV)NC1] (1). This domain is also known as the Goodpasture (auto)antigen for being the specific target of the autoantibodies mediating glomerulonephritis and lung haemorrhage in Goodpasture syndrome (2).

The GPBP-encoding gene (COL4A3BP) expresses at least three polypeptides including canonical GPBP-1, formerly called GPBP (1); GPBP-2, an alternative mRNA exon splicing isoform formerly called GPBP-26/CERT (3); and GPBP-3, a variant which results from alternative mRNA translation initiation formerly called 91-kDa GPBP (4). GPBP-1 is mainly secreted (4) and regulates type IV collagen network organization (5); GPBP-2 localizes in the cytosol (4) and regulates protein secretion (6) (i.e. type IV collagen); and GPBP-3 is attached to the external side of plasma membrane and regulates GPBP-1 exportation (4).

Increased expression of GPBP-1 at the renal glomerulus induces glomerular basement membrane (GBM) collagen disorganization and deposit of (auto)antibodies at the glomerular filtration barrier mediating glomerulonephritis (5). Moreover, increased COL4A3BP expression has been found to mediate drug-resistance in cancer cells (7), and other lines of evidence suggest that COL4A3BP products also play a role in eicosanoid synthesis and inflammation (8), in protein misfolding-mediated disorders (9), cholesterol efflux (10), protein secretory transport (6, 11) and oxidative stress and lifespan (12).

Collectively, the evidences support that COL4A3BP products regulate protein (i.e. type IV collagen) molecular and supramolecular assembly and GPBP-1, the canonical product, emerges as a new enzyme with relevance in the medical field.

Consequently, there is an increasing interest for GPBP-based patent portfolio and proprietary technology exclusively owned by FibroStatin SL.

 

References

  1. Raya A, Revert F, Navarro S, Saus J. (1999) J. Biol. Chem. 274:12642-9.
  2. Saus J, Wieslander J, Langeveld JP, Quinones S, Hudson BG. (1988) J. Biol Chem. 263:13374-80.
  3. Raya A, Revert-Ros F, Martinez-Martinez P, Navarro S, Rosello E, Vieites B, Granero F, Forteza J, Saus J. (2000) J. Biol. Chem. 275:40392-9.
  4. Revert F, Ventura I, Martínez-Martínez P, Granero-Moltó F, Revert-Ros F, Macías J, Saus J. (2008) J. Biol. Chem. 283(44):30246-55.
  5. Revert F, Merino R, Monteagudo C, Macias J, Peydró A, Alcácer J, Muniesa P, Marquina R, Blanco M, Iglesias M, Revert-Ros F, Merino J, Saus J. (2007) Am. J. Pathol. 171:1419-30.
  6. Fugmann T, Hausser A, Schöffler P, Schmid S, Pfizenmaier K, Olayioye MA. (2007) J. Cell Biol. 178:15-22.
  7. Swanton C, Marani M, Pardo O, Warne PH, Kelly G, Sahai E, Elustondo F, Chang J, Temple J, Ahmed AA, Brenton JD, Downward J, Nicke B. (2007) Cancer Cell. 11:498-512.
  8. Lamour, N. F., Stahelin, R. V., Wijesinghe, D. S., Maceyka, M., Wang, E., Allegood, J. C., Merrill, A. H. Jr., Cho, W., Chalfant, C. E. (2007) J Lipid Res. 48,1293-1304.
  9. Saus J, Revert F and Revert-Ros F (2004) "Novel Goodpasture antigen-binding protein isoforms and protein misfolded-mediated disorders" (USA) Utility Patent Application: PCT/EP04/01074 Publication nº :WO 2004/070025.
  10. Sano O, Kobayashi A, Nagao K, Kumagai K, Kioka N, Hanada K, Ueda K, Matsuo M. (2007) J. Lipid Res. 48:2377-84.
  11. Florin L, Pegel A, Becker E, Hausser A, Olayioye MA, Kaufmann H. (2009) J Biotechnol. 141:84-90.
  12. Rao RP, Yuan C, Allegood JC, Rawat SS, Edwards MB, Wang X, Merrill AH Jr, Acharya U, Acharya JK. (2007) Proc. Natl. Acad. Sci. U S A. 104:11364-9.