Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins
© 2014 Boname et al..
The regulated turnover of endoplasmic reticulum (ER)-resident membrane proteins requires their extraction from the membrane lipid bilayer and subsequent proteasome-mediated degradation. Cleavage within the transmembrane domain provides an attractive mechanism to facilitate protein dislocation but has never been shown for endogenous substrates. To determine whether intramembrane proteolysis, specifically cleavage by the intramembrane-cleaving aspartyl protease signal peptide peptidase (SPP), is involved in this pathway, we generated an SPP-specific somatic cell knockout. In a stable isotope labeling by amino acids in cell culture-based proteomics screen, we identified HO-1 (heme oxygenase-1), the rate-limiting enzyme in the degradation of heme to biliverdin, as a novel SPP substrate. Intramembrane cleavage by catalytically active SPP provided the primary proteolytic step required for the extraction and subsequent proteasome-dependent degradation of HO-1, an ER-resident tail-anchored protein. SPP-mediated proteolysis was not limited to HO-1 but was required for the dislocation and degradation of additional tail-anchored ER-resident proteins. Our study identifies tail-anchored proteins as novel SPP substrates and a specific requirement for SPP-mediated intramembrane cleavage in protein turnover.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:205 |
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| Enthalten in: |
The Journal of cell biology - 205(2014), 6 vom: 23. Juni, Seite 847-62 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boname, Jessica M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.08.2014 Date Revised 29.01.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1083/jcb.201312009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM23946480X |
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| 100 | 1 | |a Boname, Jessica M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Completed 20.08.2014 | ||
| 500 | |a Date Revised 29.01.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2014 Boname et al. | ||
| 520 | |a The regulated turnover of endoplasmic reticulum (ER)-resident membrane proteins requires their extraction from the membrane lipid bilayer and subsequent proteasome-mediated degradation. Cleavage within the transmembrane domain provides an attractive mechanism to facilitate protein dislocation but has never been shown for endogenous substrates. To determine whether intramembrane proteolysis, specifically cleavage by the intramembrane-cleaving aspartyl protease signal peptide peptidase (SPP), is involved in this pathway, we generated an SPP-specific somatic cell knockout. In a stable isotope labeling by amino acids in cell culture-based proteomics screen, we identified HO-1 (heme oxygenase-1), the rate-limiting enzyme in the degradation of heme to biliverdin, as a novel SPP substrate. Intramembrane cleavage by catalytically active SPP provided the primary proteolytic step required for the extraction and subsequent proteasome-dependent degradation of HO-1, an ER-resident tail-anchored protein. SPP-mediated proteolysis was not limited to HO-1 but was required for the dislocation and degradation of additional tail-anchored ER-resident proteins. Our study identifies tail-anchored proteins as novel SPP substrates and a specific requirement for SPP-mediated intramembrane cleavage in protein turnover | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a RNF139 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a HMOX1 protein, human |2 NLM | |
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| 650 | 7 | |a Heme Oxygenase-1 |2 NLM | |
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| 650 | 7 | |a Aspartic Acid Endopeptidases |2 NLM | |
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| 700 | 1 | |a Bloor, Stuart |e verfasserin |4 aut | |
| 700 | 1 | |a Wandel, Michal P |e verfasserin |4 aut | |
| 700 | 1 | |a Nathan, James A |e verfasserin |4 aut | |
| 700 | 1 | |a Antrobus, Robin |e verfasserin |4 aut | |
| 700 | 1 | |a Dingwell, Kevin S |e verfasserin |4 aut | |
| 700 | 1 | |a Thurston, Teresa L |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Duncan L |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Randow, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Lehner, Paul J |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:205 |g year:2014 |g number:6 |g day:23 |g month:06 |g pages:847-62 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1083/jcb.201312009 |3 Volltext |
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