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Mol. Cells 2009; 27(5): 577-582

Published online May 15, 2009

https://doi.org/10.1007/s10059-009-0078-z

© The Korean Society for Molecular and Cellular Biology

Identification of HUGT1 as a Potential BiP Activator and a Cellular Target for Improvement of Recombinant Protein Production Using a cDNA Screening System

Sebastian Chih Yuan Ku, Teng Rhui Lwa, Maybelline Giam, Miranda Gek Sim Yap, and Sheng-Hao Chao

Received: February 2, 2009; Revised: March 26, 2009; Accepted: March 27, 2009

Abstract

The development of a high-throughput functional ge-nomic screening provides a novel and expeditious ap-proach in identifying critical genes involved in specific biological processes. Here we describe a cell-based cDNA screening system to identify the transcription activators of BiP, an endoplasmic reticulum (ER) chaperone protein. BiP promoter contains the ER stress element which is commonly present in the genes involved in unfolded protein response (UPR) that regu-lates protein secretion in cells. Therefore, the positive regulators of BiP may also be utilized to improve the recombinant protein production through modulation of UPR. Four BiP activators, including human UDP-glucose:glycoprotein glucosyltransferase 1 (HUGT1), are identified by the cDNA screening. Overexpression of HUGT1 leads to a significant increase in the production of recombinant erythropoietin, interferon ?, and monoclonal antibody in HEK293 cells. Our results demonstrate that the cDNA screening for BiP activators may be effective to identify the novel BiP regulators and HUGT1 may serve as an ideal target gene for improving the recombinant protein production in mammalian cells.

Keywords HEK293, HUGT1, monoclonal antibody, recombinant protein production, unfolded protein response

Article

Research Article

Mol. Cells 2009; 27(5): 577-582

Published online May 31, 2009 https://doi.org/10.1007/s10059-009-0078-z

Copyright © The Korean Society for Molecular and Cellular Biology.

Identification of HUGT1 as a Potential BiP Activator and a Cellular Target for Improvement of Recombinant Protein Production Using a cDNA Screening System

Sebastian Chih Yuan Ku, Teng Rhui Lwa, Maybelline Giam, Miranda Gek Sim Yap, and Sheng-Hao Chao

Received: February 2, 2009; Revised: March 26, 2009; Accepted: March 27, 2009

Abstract

The development of a high-throughput functional ge-nomic screening provides a novel and expeditious ap-proach in identifying critical genes involved in specific biological processes. Here we describe a cell-based cDNA screening system to identify the transcription activators of BiP, an endoplasmic reticulum (ER) chaperone protein. BiP promoter contains the ER stress element which is commonly present in the genes involved in unfolded protein response (UPR) that regu-lates protein secretion in cells. Therefore, the positive regulators of BiP may also be utilized to improve the recombinant protein production through modulation of UPR. Four BiP activators, including human UDP-glucose:glycoprotein glucosyltransferase 1 (HUGT1), are identified by the cDNA screening. Overexpression of HUGT1 leads to a significant increase in the production of recombinant erythropoietin, interferon ?, and monoclonal antibody in HEK293 cells. Our results demonstrate that the cDNA screening for BiP activators may be effective to identify the novel BiP regulators and HUGT1 may serve as an ideal target gene for improving the recombinant protein production in mammalian cells.

Keywords: HEK293, HUGT1, monoclonal antibody, recombinant protein production, unfolded protein response

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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