Production of Cells with Targeted Integration of Gene Variants of Human ABC Transporter for Stable and Regulated Expression Using the Flp Recombinase System - Protein Misfolding and Cellular Stress in Disease and Aging - page 136

Fig. 1. Schematic illustration of protein folding and quality control in the ER and plausible pathways for degradation of
ABCG2. BiP and CNX with their accessory proteins, for example, glucosidases I and II, and PDI, associate with the nascent
peptide of ABCG2, as soon as the nascent peptide enters the ER lumen. When the ABCG2 protein has acquired its cor-
rectly folded structure with disulfide bonds and N -linked glycan, it is ready for exit from the ER and transfer to the ERGIC
and Golgi for further processing. The ER-to- Golgi traffic may be mediated by COPII/Sar1p. The correctly processed ABCG2
WT is finally destined to reach the plasma membrane and is then degraded by the endosome-lysosome pathway after
remaining in the plasma membrane domain for a certain period. In contrast, the misfolded ABCG2 protein undergoes
ubiquitination-mediated proteasomal degradation. During the ERAD process, chaperones, such as Hsp90, Hsp70, Hsp40,
CHIP, p23, Aha1, FKBP8, and/or Jab1/CSN5, may recruit E3 ubiquitin ligase and facilitate the ubiquitination of the mis-
folded ABCG2 protein. Bafilomycin A 1 (BMA) and MG132 inhibit lysosomal and proteasomal degradation, respectively.
location in mammalian host cells ( 28-34 ). At present, the
Flp-In TM system is commercially available from Invitrogen
(Carlsbad, CA, USA: www.invitrogen.com).
(b) Flp-In TM cell lines (Invitrogen, Carlsbad, CA, USA) were
generated from the American Type Culture Collection