Words similar to importin-β
Example sentences for: importin-β
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6) and importin-β (Fig.
Aside from its well-characterized role in protein folding [ 66 ] , Hsp70 is known to associate with the GR in the cytoplasm, where it promotes formation of a heterocomplex between the inactive GR and Hsp90 [ 67 ] . In addition, Hsp70 becomes concentrated in the nucleus when cells are exposed to environmental stress [ 68 ] . Of particular note, the nuclear accumulation of the Hsp70, Ssa4p, in response to nutrient deprivation in yeast appears to occur by a novel mechanism that involves its direct interaction with Mmd5p, a member of the importin-β family [ 69 ] . A role for Rab24 in nuclear trafficking would be unanticipated, since the only GTPase known to function in nuclear import/export (Ran) is structurally distinct from the Rab subgroup of the Ras superfamily [ 70 71 ] . Nevertheless, we can speculate that if Rab24 participates in a stress-induced pathway for nuclear import of Hsp70 in mammalian cells, the constitutive overexpression of Rab24(D123I) might stimulate aberrant accumulation of Hsp70/importin-β aggregates at the nuclear pore complex.
The possibility that the inclusions induced by mycRab24(D123I) contain aggregated nuclear import complexes was further supported by immuno-staining with an antibody against importin-β (karyopherin-β), which revealed focal concentrations of importin-β in these structures (Fig.
Rab24 contains a unique arginine-rich insert, 126EEDRRRRR 133 [ 25 ] in the domain cognate to loop-8 in H-Ras [ 34 ] . The latter sequence is reminiscent of unusual arginine-rich nuclear localization signals that allow proteins like HIV tet and rev to undergo nuclear translocation by association with importin-β, in the absence of importin-α [ 45 46 ] . Since the loop-8 insert in Rab24 lies adjacent to the conserved N(T)KxD nucleotide binding cassette, we hypothesized that conformational changes caused by the D123I substitution might render the Rab24 mutant capable of disrupting the nuclear import machinery [ 47 ] . To test this possibility, we co-expressed mycRab24wt or mycRab24(D123I) with GR-GFP, a fusion between the glucocorticoid receptor and green fluorescent protein.
The inclusions bear a superficial resemblance to those described in some of the polyglutamine disorders, and appear to sequester Hsp70, ubiquitin, importin-β, and glucocorticoid receptor.
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