A luminal flavoprotein in endoplasmic reticulum-associated degradation

TY - JOUR

T1 - A luminal flavoprotein in endoplasmic reticulum-associated degradation

AU - Riemer, Jan

AU - Appenzeller-Herzog, Christian

AU - Johansson, Linda

AU - Bodenmiller, Bernd

AU - Hartmann-Petersen, Rasmus

AU - Ellgaard, Lars

N1 - Keywords: Amino Acid Sequence; Cell Line; Endoplasmic Reticulum; Flavoproteins; Glycosylation; HSP40 Heat-Shock Proteins; Humans; Molecular Chaperones; Molecular Sequence Data; Neoplasm Proteins; Protein Binding; Proteins; Sequence Alignment; Ubiquitination

PY - 2009

Y1 - 2009

N2 - The quality control system of the endoplasmic reticulum (ER) discriminates between native and nonnative proteins. The latter are degraded by the ER-associated degradation (ERAD) pathway. Whereas many cytosolic and membrane components of this system are known, only few luminal players have been identified. In this study, we characterize ERFAD (ER flavoprotein associated with degradation), an ER luminal flavoprotein that functions in ERAD. Upon knockdown of ERFAD, the degradation of the ERAD model substrate ribophorin 332 is delayed, and the overall level of polyubiquitinated cellular proteins is decreased. We also identify the ERAD components SEL1L, OS-9 and ERdj5, a known reductase of ERAD substrates, as interaction partners of ERFAD. Our data show that ERFAD facilitates the dislocation of certain ERAD substrates to the cytosol, and we discuss the findings in relation to a potential redox function of the protein.

AB - The quality control system of the endoplasmic reticulum (ER) discriminates between native and nonnative proteins. The latter are degraded by the ER-associated degradation (ERAD) pathway. Whereas many cytosolic and membrane components of this system are known, only few luminal players have been identified. In this study, we characterize ERFAD (ER flavoprotein associated with degradation), an ER luminal flavoprotein that functions in ERAD. Upon knockdown of ERFAD, the degradation of the ERAD model substrate ribophorin 332 is delayed, and the overall level of polyubiquitinated cellular proteins is decreased. We also identify the ERAD components SEL1L, OS-9 and ERdj5, a known reductase of ERAD substrates, as interaction partners of ERFAD. Our data show that ERFAD facilitates the dislocation of certain ERAD substrates to the cytosol, and we discuss the findings in relation to a potential redox function of the protein.

U2 - 10.1073/pnas.0900742106

DO - 10.1073/pnas.0900742106

M3 - Journal article

C2 - 19706418

SN - 0027-8424

VL - 106

SP - 14831

EP - 14836

JO - Proceedings of the National Academy of Science of the United States of America

JF - Proceedings of the National Academy of Science of the United States of America

IS - 35

ER -