The non-classical export routes: FGF1 and IL-1alpha point the way.
Non-classical protein release independent of the ER-Golgi pathway has been reported for an increasing number of proteins lacking an N-terminal signal sequence. The export of FGF1 and IL-1alpha, two pro-angiogenic polypeptides, provides two such examples. In both cases, export is based on the Cu2+-dependent formation of multiprotein complexes containing the S100A13 protein and might involve translocation of the protein across the membrane as a 'molten globule'. FGF1 and IL-1alpha are involved in pathological processes such as restenosis and tumor formation. Inhibition of their export by Cu2+ chelators is thus an effective strategy for treatment of several diseases.
Prudovsky
Igor
I
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, Maine 04074, USA.
Mandinova
Anna
A
Soldi
Raffaella
R
Bagala
Cinzia
C
Graziani
Irene
I
Landriscina
Matteo
M
Tarantini
Francesca
F
Duarte
Maria
M
Bellum
Stephen
S
Doherty
Holly
H
Maciag
Thomas
T
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008560:Membrane Fluidity / Q000502:physiology; D008961:Models, Structural; D009389:Neovascularization, Pathologic / Q000378:metabolism; D021382:Protein Sorting Signals / Q000502:physiology*; D021381:Protein Transport; D009418:S100 Proteins
D007375:Interleukin-1; D021382:Protein Sorting Signals; D009418:S100 Proteins; C511523:S100A13 protein, human; D016220:Fibroblast Growth Factor 1; D003300:Copper