Bap29varP, a variant of Bap29, influences the cell surface expression of the human P-glycoprotein.
P-glycoprotein (Pgp), a plasma membrane (PM) glycoprotein, is responsible for the development of multidrug resistance. The mechanism by which Pgp is targeted to the PM is not defined. To identify proteins that influence Pgp trafficking, we utilized the yeast two-hybrid analysis procedure, which identified a new isoform of endoplasmic reticulum (ER)-bound Bap29, termed Bap29varP, as an interacting protein with the N-terminus of Pgp. The drug-resistant human breast cancer MCF-7 (MCF-7/Adr(R)) cells express both Bap29varP and approximately 170 kDa Pgp, which are however absent in the drug-sensitive MCF-7 cells. When Bap29varP was overexpressed in MCF-7/Adr(R) cells, Pgp was predominantly localized in the ER and intracellular vesicles, suggesting Bap29varP influences Pgp trafficking. When Pgp was expressed in MCF-7 cells, it was exclusively found in the ER with a molecular mass of approximately 160 kDa slightly smaller than that of the molecular mass of Pgp expressed in MCF-7/Adr(R) cells. On the other hand, when Pgp was expressed in Bap29varP-containing human colon adenocarcinoma HT-29 cells, it was localized at the PM. These findings together suggest that Bap29varP acts as an essential chaperone, influencing the processing and trafficking of Pgp to the cell surface.
Rao
Prema S
PS
The Anticancer Resistance Research Group and The Cancer Biology Center, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA. us.rao@ttuhsc.edu
Bickel
Ulrich
U
Srivenugopal
Kalkunte S
KS
Rao
U Subrahmanyeswara
US
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D011960:Receptors, Estrogen / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C486244:BCAP29 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; D011960:Receptors, Estrogen