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Engineering responsiveness to cell culture stresses: Growth arrest and DNA damage gene 153 ( GADD153 ) and the unfolded protein response (UPR) in NS0 myeloma cells
Author(s) -
Cudna Renata E.,
Dickson Alan J.
Publication year - 2006
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.20861
Subject(s) - unfolded protein response , endoplasmic reticulum , apoptosis , dna damage , microbiology and biotechnology , biology , programmed cell death , gene , dna , genetics
Abstract The successful movement of a newly synthesized protein through the endoplasmic reticulum (ER) and associated membranous compartments is dependent on appropriate recognition by complex processing systems. Failure to perceive appropriately processed or modified intermediates in the pathway can initiate a series of cellular signaling events (ER stress or unfolded protein response, UPR) that can lead to cell apoptosis and loss of biomass in culture processes. We have shown that expression of growth arrest and DNA damage gene 153 ( GADD153 ) is associated with recognition of damaged or mis‐processed proteins within the secretory processes of CHO and NS0 myeloma cells. To directly characterize the roles of GADD153 in UPR‐directed apoptosis, we have generated stable clones of NS0 myeloma cells with elevated (constitutive and inducible) and deleted GADD153 expression. Although GADD153 is a robust indicator of the onset of ER stress or the UPR, GADD153 expression alone is not sufficient to provoke NS0 myeloma apoptosis and it is not required for apoptosis to occur. © 2006 Wiley Periodicals, Inc.