ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family.
In human cells, Ero1-Lalpha and -Lbeta (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-Lalpha. 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-Lalpha redox isoforms, suggesting that ERp44 may be involved in the control of oxidative protein folding.
Anelli
Tiziana
T
DiBiT-HSR and Università Vita-Salute San Raffaele, Via Olgettina 58, I-20132 Milan, Italy.
Alessio
Massimo
M
Mezghrani
Alexandre
A
Simmen
Thomas
T
Talamo
Fabio
F
Bachi
Angela
A
Sitia
Roberto
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D002155:Calsequestrin / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry
D002155:Calsequestrin; D002352:Carrier Proteins; D017931:DNA Primers; C451899:ERP44 protein, human; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D013879:Thioredoxins