Sequestration of the abrin A chain to the nucleus by BASP1 increases resistance of cells to abrin toxicity

Abrin, a type II ribosome inactivating protein, comprises of A and B subunits wherein the A subunit harbors toxin activity and the B subunit has galactose-specific lectin activity. The entry of the protein inside the cell is through the binding of the B chain to cell surface glycoproteins followed by receptor-mediated endocytosis and retrograde transport. An earlier study from our laboratory showed that different cell lines exhibited differences of as much as ~ 200-fold in abrin toxicity prompting studies to compare the trafficking of the toxin within cells. Observations made in this regard revealed that the abrin A chain, after being released into the cytosol, is sequestered into the nucleus through an interaction with a cytosolic protein of ~25 kDa, the Brain acid-soluble protein 1 (BASP1). The nuclear localization of the A chain is seen predominantly in cells that are less sensitive to abrin toxicity and dependent on the levels of BASP1 in cells. The sequestration by BASP1 renders cells increasingly resistant to the inhibition of protein synthesis by abrin and the nucleus may be acting as a sink to overcome cellular stress induced by the toxin.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research