Mutational studies of G553 in TM5 of ABCG2: a residue potentially involved in dimerization.

Biochemistry
Orsolya PolgarSusan E Bates

Abstract

ABCG2 is an ATP-binding cassette half-transporter conferring resistance to chemotherapeutic agents such as mitoxantrone, irinotecan, and flavopiridol. With its one transmembrane and one ATP-binding domain, ABCG2 is thought to homodimerize for function. One conserved region potentially involved in dimerization is a three-amino acid sequence in transmembrane segment 5 (residues 552-554). Mutations in the corresponding residues in the Drosophila white protein (an orthologue of ABCG2) are thought to disrupt heterodimerization. We substituted glycine 553 with leucine (G553L) followed by stable transfection in HEK 293 cells. The mutant was not detectable on the cell surface, and markedly reduced protein expression levels were observed by immunoblotting. A deficiency in N-linked glycosylation was suggested by a reduction in molecular mass compared to that of the 72 kDa wild-type ABCG2. Similar results were observed with the G553E mutant. Confocal microscopy demonstrated mostly ER localization of the G553L mutant in HEK 293 cells, even when coexpressed with the wild-type protein. Despite its altered localization, the G553L and G553E mutants were cross-linked using amine-reactive cross-linkers with multiple arm lengths, suggesting that ...Continue Reading

References

Jan 26, 1996·The Journal of Biological Chemistry·M MüllerB Sarkadi
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·H W van VeenW N Konings
Aug 7, 1998·Biochimica Et Biophysica Acta·H W van Veen, W N Konings
Dec 28, 1999·Glycoconjugate Journal·F AltmannL März
Feb 13, 2001·Biochemical and Biophysical Research Communications·S KawabataS Kohno
Jul 5, 2001·Biochemical and Biophysical Research Communications·C OzvegyB Sarkadi
Jan 25, 2002·International Journal of Cancer. Journal International Du Cancer·Kumie KageYoshikazu Sugimoto
Sep 5, 2002·The Journal of Clinical Investigation·Gregory A GrafHelen H Hobbs
Sep 13, 2002·Biochimica Et Biophysica Acta·Thomas LitmanSusan E Bates
Oct 24, 2002·Blood·Brian L AbbottBrian P Sorrentino
Sep 25, 2003·The Journal of Biological Chemistry·Gregory A GrafHelen H Hobbs
Dec 20, 2003·Nature·Roberto Sitia, Ineke Braakman
Feb 21, 2004·Cancer Biology & Therapy·Gergely SzakácsMichael M Gottesman
Apr 1, 2004·The Journal of Biological Chemistry·Gregory A GrafHelen H Hobbs
Jul 9, 2004·Biochemical and Biophysical Research Communications·Judit CserepesN Barry Elkind
Jul 21, 2004·Biochemistry·Orsolya PolgarSusan E Bates
Jan 26, 2005·Biochemical Society Transactions·O Polgar, S E Bates
Aug 19, 2005·The Journal of Biological Chemistry·Ulla HenriksenUlrik Gether

❮ Previous
Next ❯

Citations

Aug 14, 2010·The Journal of Biological Chemistry·Elodie Desuzinges-MandonPierre Falson
Mar 6, 2010·The Journal of Pharmacology and Experimental Therapeutics·Xiaokun CaiQingcheng Mao
Apr 30, 2014·Archives of Toxicology·Márton JaniPéter Krajcsi
Mar 29, 2008·Expert Opinion on Drug Metabolism & Toxicology·Orsolya PolgarSusan E Bates
Jan 7, 2009·Advanced Drug Delivery Reviews·Christopher A McDevittRichard Callaghan
Jan 13, 2009·Advanced Drug Delivery Reviews·Robert W RobeySusan E Bates
Nov 4, 2008·Protein Expression and Purification·Alexandre PozzaAttilio Di Pietro
Feb 6, 2008·Journal of Structural Biology·Eszter Hazai, Zsolt Bikádi
Nov 10, 2006·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Yehuda G Assaraf
Dec 28, 2010·Biochemical and Biophysical Research Communications·Takashi SugiyamaHirofumi Kai
May 2, 2009·Biochimica Et Biophysica Acta·Orsolya PolgarSusan E Bates
Sep 4, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Johanna Troberg, Moshe Finel
Sep 12, 2013·Molecular Pharmacology·Alexandra E StacyDes R Richardson
Mar 4, 2008·The Journal of Experimental Biology·Jennifer M EvansShireen-Anne Davies

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.