mTORC1 Links Protein Quality and Quantity Control by Sensing Chaperone Availability
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15 citations
Cites background or result from "mTORC1 Links Protein Quality and Qu..."
...To prevent proteotoxicity from increased protein misfolding, cells rely on the function of numerous heat shock proteins (Hsps), including Hsp70 and Hsp40 (Li and Laszlo, 1985; Ananthan et al., 1986; Watowich and Morimoto, 1988; Hightower, 1991; Trotter et al., 2002; Barrett et al., 2004)....
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..., 2010) and alterations in global protein synthesis (Kretz-Remy et al., 1998; Qian et al., 2010)....
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...Such data imply that Hsps are potentially overwhelmed or insufficient in this model of toxicity or conversely raise the possibility of protein misfolding being capable of initiating cell death independently of Hsp-regulated events....
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...Both Can and AZC have been shown to induce a variety of Hsps (Thomas and Mathews, 1984; Li and Laszlo, 1985; Watowich and Morimoto, 1988; Kozutsumi et al., 1998; Trotter et al., 2002; Qian et al., 2010), consistent with both analogs promoting proteotoxic stress....
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...Next, we sought to elucidate whether Can and AZC treatment altered the levels of Hsps in neurons and astrocytes....
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15 citations
Cites background or result from "mTORC1 Links Protein Quality and Qu..."
...The stimulation of protein synthesis observed at low puromycin concentrations is consistent with previous reports demonstrating that moderate accumulation of misfolded proteins induces a small increase in protein synthesis [29]....
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...1A), which we speculate is a response to low levels of misfolded polypeptides [29]....
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14 citations
12 citations
Cites background from "mTORC1 Links Protein Quality and Qu..."
...In turn, HSF1 has been shown to regulate mTORC1 activity during stress and to stimulate rDNA transcription in cancer cells, thus suggesting that it may bolster translation.(99,114) In addition to HSF1, SKN-1 (C....
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...2A).(99) This suggests that a reduction in chaperone availability during moderate stress may modulate mTORC1 activity....
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...Recent observations suggest that partial reduction in availability of the chaperone Hsp90 during the early stress response stimulates mTORC1 signaling, whereas prolonged exposure to stress that exceeds buffering capacity of the chaperones appears to inhibit mTORC1 activity.(99) Depletion of chaperone function by genetic (loss of heat shock factor protein 1 [HSF1]) or pharmacological means (using the Hsp90 inhibitor geldanamycin) resulted in a more rapid inhibition of mTORC1 signaling during the course of stress as compared with control cells (Fig....
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12 citations
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