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 -