title: Sequestration of the abrin A chain to the nucleus by BASP1 increases the resistance of cells to abrin toxicity.
abstract: Abrin, a type II ribosome-inactivating protein, comprises A and B subunits wherein the A subunit harbours toxin activity and the B subunit has a 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. A previous study from our laboratory showed that different cell lines exhibited differences of as great as ~200-fold in abrin toxicity, prompting the present study 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 interaction with a cellular protein of ~25 kDa, BASP1 (brain acid-soluble protein 1). 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 act as a sink to overcome cellular stress induced by the toxin.
authors.affiliation: *Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, Pin 560012, India.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Gadadhar
authors.affiliation: *Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, Pin 560012, India.
authors.forename: Namrata
authors.initials: N
authors.lastname: Bora
authors.affiliation: *Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, Pin 560012, India.
authors.forename: Vinita
authors.initials: V
authors.lastname: Tiwari
authors.affiliation: *Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, Pin 560012, India.
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Karande
mesh_terms: D000036:Abrin / Q000378:metabolism* / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism*; D004351:Drug Resistance / Q000502:physiology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C104089:BASP1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D000036:Abrin