The endoplasmic reticulum as a protein-folding compartment

Helenius, Ari; Marquardt, Thorsten; Braakman, Ineke

doi:10.1016/0962-8924(92)90309-b

Cited by 293 publications

(199 citation statements)

References 42 publications

(2 reference statements)

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“…The cleavage of the signal peptide by signal peptidase occurs rapidly thereafter. It is in the RER that secretory proteins will become folded into their tertiary structure, assisted by chaperone proteins [6][7][8][9][10][11]. Oligomerization also occurs in this compartment [8].…”

Section: Protein Secretory Pathways: a General Outline Leader And Leamentioning

confidence: 99%

Sorting and processing of secretory proteins

Halban

Irminger

1994

Biochemical Journal

307

226

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Section: Protein Secretory Pathways: a General Outline Leader And Leamentioning

confidence: 99%

Sorting and processing of secretory proteins

Halban

Irminger

1994

Biochemical Journal

307

226

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“…Newly synthesized secretory and transmembrane proteins are folded and assembled in the endoplasmic reticulum (ER), where an efficient quality control system operates (Gething and Sambrook, 1992;Helenius et al, 1992). Under a variety of conditions collectively termed ER stress, however, the quality control system is hampered, resulting in the accumulation of unfolded proteins in the ER.…”

Section: Introductionmentioning

confidence: 99%

Analysis of ATF6 Activation in Site-2 Protease-deficient Chinese Hamster Ovary Cells

Nadanaka

Yoshida

Sato

et al. 2006

Cell Struct. Funct.

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ABSTRACT. Mammalian transcription factor ATF6 is constitutively synthesized as a type II transmembrane protein embedded in the endoplasmic reticulum (ER). It is activated when unfolded proteins are accumulated in the ER under ER stress through a process called regulated intramembrane proteolysis (Rip), in which ATF6 is transported from the ER to the Golgi apparatus where it undergoes sequential cleavage by Site-1 and Site-2 proteases. The cytosolic transcription factor domain of ATF6 liberated from the Golgi membrane enters the nucleus where it activates transcription of ER-localized molecular chaperones and folding enzymes, leading to the maintenance of the homeostasis of the ER. Here, we analyzed M19 cells, a mutant of Chinese hamster ovary cells deficient in Site-2 protease. It was previously shown that M19 cells are defective in the induction of mRNA encoding the major ER chaperone BiP. In M19 cells, ATF6 was not converted from the membrane-bound precursor form to the cleaved and nuclear form as expected. Moreover, some of the ATF6 was constitutively relocated to the Golgi apparatus, where it was cleaved by Site-1 protease, and remained associated with the Golgi apparatus, indicating that the ER of M19 cells was constitutively stressed. Consistent with this notion, the two other ER stress response mediators, IRE1 and PERK, were also constitutively activated in M19 cells. M19 cells showed inefficient secretion of a model protein. These results suggest that Rip-mediated activation of ATF6 is important for the homeostasis of the ER in not only ER-stressed but also unstressed cells.

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“…DsbA is regenerated into the active oxidized form by DsbB, an integral membrane protein, in which reoxidation is linked to the respiratory chain (16 -18). In eukaryotic cells, oxidative protein folding occurs in the ER (2), and work in yeast suggests that a similar chain of events takes place in this organelle. Proteins enter the ER in the reduced state and rapidly form disulfide bonds, often when the nascent chain is still bound to the ribosome (19 folding, a crucial step in the maturation of many secretory and membrane proteins.…”

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confidence: 99%

“…Proteins that do not fulfill these requirements are selectively retained and eventually dislocated across the ER membrane to be degraded by cytosolic proteasomes. These processes are regulated by a vast array of ER-resident chaperones and enzymes (1,2).…”

mentioning

confidence: 99%