Systems biology of the mammalian Unfolded Protein Response

Systems biology of unfolded protein response in recombinant CHO cells

Background Productivity of recombinant therapeutics is a coordinated effort of multiple pathways in the cell [1]. The protein processing pathway in endoplasmic reticulum has been the target of many cell engineering studies but with mixed results [2]. We have observed the induction of UPR genes in recombinant CHO cells (data not shown). In this work, we attempt to increase their productivity fur...

Mechanistic Modeling and Analysis of the Mammalian Unfolded Protein Response

Cells monitor protein folding by an inbuilt quality-control system in which incorrectly or misfolded folded proteins are tagged for degradation or sent back through a refolding cycle. However, continued accumulation of incorrectly folded proteins triggers the Unfolded Protein Response (UPR), which attempts to re-establish folding homeostasis or commits the cell to apoptosis. In this study, we d...

The unfolded protein response

Where does the UPR function? Between the endoplasmic reticulum (ER) and the nucleus of eukaryotic cells. All secreted proteins and proteins that reside in secretory compartments translocate as nascent peptide chains into the ER, where they may undergo folding, modification and assembly before assuming their functional conformations. The ER maintains a specialized oxidizing environment to aid ch...

The unfolded protein response.

The endoplasmic reticulum (ER) is a principal site for folding and maturation of transmembrane, secretory and ERresident proteins. Perturbations that alter ER homeostasis can lead to accumulation of unfolded proteins (UPs), which is a threat to all living cells. To cope with the stress, cells activate an intracellular signaling pathway – the unfolded protein response (UPR). The UPR is an integr...

SnapShot: The Unfolded Protein Response