ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family

Tiziana Anelli, Massimo Alessio, Alexandre Mezghrani, Thomas Simmen, Fabio Talamo, Angela Bachi, Roberto Sitia

Research output: Contribution to journalArticle

188 Citations (Scopus)

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 languageEnglish
Pages (from-to)835-844
Number of pages10
JournalEMBO Journal
Volume21
Issue number4
DOIs
Publication statusPublished - Feb 15 2002

Fingerprint

Thioredoxins
Endoplasmic Reticulum
Protein folding
Protein Folding
Disulfides
Oxidation-Reduction
Proteins
Protein Disulfide-Isomerases
Endoplasmic Reticulum Stress
Proteasome Endopeptidase Complex
Isomerization
Cysteine
Protein Isoforms
Cells
Molecules

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 journalArticle

Anelli, Tiziana ; Alessio, Massimo ; Mezghrani, Alexandre ; Simmen, Thomas ; Talamo, Fabio ; Bachi, Angela ; Sitia, Roberto. / ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. In: EMBO Journal. 2002 ; Vol. 21, No. 4. pp. 835-844.
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