Abstract
In human cells, Ero1-Lα and -Lβ (hEROs) regulate oxidative protein folding by selectively oxidizing protein disulfide isomerase. Specific protein-protein interactions are probably crucial for regulating the formation, isomerization and reduction of disulfide bonds in the endoplasmic reticulum (ER). To identify molecules involved in ER redox control, we searched for proteins interacting with Ero1-Lα. Here, we characterize a novel ER resident protein (ERp44), which contains a thioredoxin domain with a CRFS motif and is induced during ER stress. ERp44 forms mixed disulfides with both hEROs and cargo folding intermediates. Whilst the interaction with transport-competent Ig-K chains is transient, ERp44 binds more stably with J chains, which are retained in the ER and eventually degraded by proteasomes. ERp44 does not bind a short-lived ribophorin mutant lacking cysteines. Its overexpression alters the equilibrium of the different Ero1-Lα redox isoforms, suggesting that ERp44 may be involved in the control of oxidative protein folding.
| Original language | English |
|---|---|
| Pages (from-to) | 835-844 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 21 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 15 2002 |
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Keywords
- Endoplasmic reticulum
- Isomerase
- Oxidative protein folding
- Redox control
- Unfolded protein response
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. / Anelli, Tiziana; Alessio, Massimo; Mezghrani, Alexandre; Simmen, Thomas; Talamo, Fabio; Bachi, Angela; Sitia, Roberto.
In: EMBO Journal, Vol. 21, No. 4, 15.02.2002, p. 835-844.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family
AU - Anelli, Tiziana
AU - Alessio, Massimo
AU - Mezghrani, Alexandre
AU - Simmen, Thomas
AU - Talamo, Fabio
AU - Bachi, Angela
AU - Sitia, Roberto
PY - 2002/2/15
Y1 - 2002/2/15
N2 - In human cells, Ero1-Lα and -Lβ (hEROs) regulate oxidative protein folding by selectively oxidizing protein disulfide isomerase. Specific protein-protein interactions are probably crucial for regulating the formation, isomerization and reduction of disulfide bonds in the endoplasmic reticulum (ER). To identify molecules involved in ER redox control, we searched for proteins interacting with Ero1-Lα. Here, we characterize a novel ER resident protein (ERp44), which contains a thioredoxin domain with a CRFS motif and is induced during ER stress. ERp44 forms mixed disulfides with both hEROs and cargo folding intermediates. Whilst the interaction with transport-competent Ig-K chains is transient, ERp44 binds more stably with J chains, which are retained in the ER and eventually degraded by proteasomes. ERp44 does not bind a short-lived ribophorin mutant lacking cysteines. Its overexpression alters the equilibrium of the different Ero1-Lα redox isoforms, suggesting that ERp44 may be involved in the control of oxidative protein folding.
AB - In human cells, Ero1-Lα and -Lβ (hEROs) regulate oxidative protein folding by selectively oxidizing protein disulfide isomerase. Specific protein-protein interactions are probably crucial for regulating the formation, isomerization and reduction of disulfide bonds in the endoplasmic reticulum (ER). To identify molecules involved in ER redox control, we searched for proteins interacting with Ero1-Lα. Here, we characterize a novel ER resident protein (ERp44), which contains a thioredoxin domain with a CRFS motif and is induced during ER stress. ERp44 forms mixed disulfides with both hEROs and cargo folding intermediates. Whilst the interaction with transport-competent Ig-K chains is transient, ERp44 binds more stably with J chains, which are retained in the ER and eventually degraded by proteasomes. ERp44 does not bind a short-lived ribophorin mutant lacking cysteines. Its overexpression alters the equilibrium of the different Ero1-Lα redox isoforms, suggesting that ERp44 may be involved in the control of oxidative protein folding.
KW - Endoplasmic reticulum
KW - Isomerase
KW - Oxidative protein folding
KW - Redox control
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=0037083869&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037083869&partnerID=8YFLogxK
U2 - 10.1093/emboj/21.4.835
DO - 10.1093/emboj/21.4.835
M3 - Article
C2 - 11847130
AN - SCOPUS:0037083869
VL - 21
SP - 835
EP - 844
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 4
ER -