The AAA-ATPase ((A) under bar TPase (a) under bar ssociated with various cellular (a) under bar ctivities) p97 has been implicated in the degradation of misfolded and unassembled proteins in the endoplasmic reticulum (ERAD). To better understand its role in this process, we used a reconstituted cell-free system to define the precise contribution of p97 in degrading immature forms of the polytopic, multi-domain protein CFTR (cystic fibrosis transmembrane conductance regulator). Although p97 augmented both the rate and the extent of CFTR degradation, it was not obligatorily required for ERAD. Only a 50% decrease in degradation was observed in the complete absence of p97. Moreover, p97 specifically stimulated the degradation of CFTR transmembrane (TM) domains but had no effect on isolated cytosolic domains. Consistent with this, p97-mediated extraction of intact TM domains was independent of proteolytic cleavage and influenced by TM segment hydrophobicity, indicating that the relative contribution of p97 is partially determined by substrate stability. Thus, we propose that p97 functions in ERAD as a nonessential but important ancillary component to the proteasome where it facilitates substrate presentation and increases the degradation rate and efficiency of stable ( TM) domains.
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Babbitt, SE
Kiss, A
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Kiss, A
Deffenbaugh, AE
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Deffenbaugh, AE
Chang, YH
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Chang, YH
Bailly, E
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Bailly, E
Erdjument-Bromage, H
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Erdjument-Bromage, H
Tempst, P
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h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Tempst, P
Buranda, T
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h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Buranda, T
Sklar, LA
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h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Sklar, LA
Baumler, J
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Baumler, J
Gogol, E
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机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Gogol, E
Skowyra, D
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h-index: 0
机构:
St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USASt Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Bays, NW
Wilhovsky, SK
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h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Wilhovsky, SK
Goradia, A
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h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Goradia, A
Hodgkiss-Harlow, K
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h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Hodgkiss-Harlow, K
Hampton, RY
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h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Dai, RM
Chen, EY
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h-index: 0
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Chen, EY
Longo, DL
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h-index: 0
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Longo, DL
Gorbea, CM
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h-index: 0
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Gorbea, CM
Li, CCH
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h-index: 0
机构:
NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USANCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Dalal, S
Rosser, MFN
论文数: 0引用数: 0
h-index: 0
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Rosser, MFN
Cyr, DM
论文数: 0引用数: 0
h-index: 0
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Cyr, DM
Hanson, PI
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Babbitt, SE
Kiss, A
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Kiss, A
Deffenbaugh, AE
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Deffenbaugh, AE
Chang, YH
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Chang, YH
Bailly, E
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Bailly, E
Erdjument-Bromage, H
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Erdjument-Bromage, H
Tempst, P
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Tempst, P
Buranda, T
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Buranda, T
Sklar, LA
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Sklar, LA
Baumler, J
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Baumler, J
Gogol, E
论文数: 0引用数: 0
h-index: 0
机构:St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
Gogol, E
Skowyra, D
论文数: 0引用数: 0
h-index: 0
机构:
St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USASt Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Bays, NW
Wilhovsky, SK
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Wilhovsky, SK
Goradia, A
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Goradia, A
Hodgkiss-Harlow, K
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
Hodgkiss-Harlow, K
Hampton, RY
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USAUniv Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Dai, RM
Chen, EY
论文数: 0引用数: 0
h-index: 0
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Chen, EY
Longo, DL
论文数: 0引用数: 0
h-index: 0
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Longo, DL
Gorbea, CM
论文数: 0引用数: 0
h-index: 0
机构:NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
Gorbea, CM
Li, CCH
论文数: 0引用数: 0
h-index: 0
机构:
NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USANCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Dalal, S
Rosser, MFN
论文数: 0引用数: 0
h-index: 0
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Rosser, MFN
Cyr, DM
论文数: 0引用数: 0
h-index: 0
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Cyr, DM
Hanson, PI
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA