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Example sentences for: misfolded
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Interestingly, Rab24 has been implicated as a possible mediator of autophagy in a recent study where wild-type GFP-Rab24 was observed to accumulate on large autophagic vacuoles in cells subjected to amino acid starvation [ 43 ] . Thus, if Rab24(D123I) functions as a true dominant suppressor of endogenous Rab24, the inclusions observed in the present study may consist of misfolded endogenous proteins that cannot be degraded because basal activity of the autophagosome-lysosome pathway is blocked.
Indeed, a similar explanation has been invoked to explain the presence of Hsp70 and ubiquitin in nuclear aggregates observed in cells expressing abnormal gene products with poly-Gln tracts, such as huntingtin [ 54 ] and ataxin-1 [ 59 ] . Based on reports that overexpression of chaperones [ 59 62 ] or a dominant-negative form of the ubiquitin-conjugating enzyme [ 63 ] can suppress the formation of poly-Gln protein aggregates, Kaytor and Warren [ 58 ] proposed a three-stage model wherein (i) molecular chaperones initially associate with the misfolded protein, (ii) failure to diminish the pool of misfolded protein leads to aggregation and ubiquitination and (iii) inefficient degradation of the aggregate by the proteasome is manifested by the accumulation of inclusion bodies.
The present results further highlight the unique nature of Rab24 and raise the possibility that it may function in autophagic degradation of misfolded proteins, or perhaps play an unanticipated role in nuclear protein trafficking or maintenance/assembly of the nuclear envelope.
Between these two effects, it is likely that cells with aggregated α-synuclein will become less able to handle damaged or misfolded proteins.
These large spots were reminiscent of recently described aggresomes, accumulations of misfolded protein that are being targeted for proteasome-dependent degradation [ 17 18 ] . This observation suggested the possibility that intracellular localization of sα i2 may reflect targeting to a proteasome-dependent degradative pathway.
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