ABCMdb

ABCG2 p.Leu554Pro

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Publications

PMID: 11807788 [PubMed] Kage K et al: "Dominant-negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S-S dependent homodimerization."

No. Sentence Comment

9 Next, inactive BCRP cDNA clones were introduced to MycBCRP-transfected cells and tested for the ability to lower drug resistance. Among the 8 inactive mutant cDNA clones tested, HABCRP cDNA clone 15 with an amino acid change from Leu to Pro at residue 554 in the fifth transmembrane domain of BCRP partially reversed the drug resistance of MycBCRP-transfected cells. Login to comment
94 Next, these 8 inactive HABCRP cDNA clones were introduced to PA/MycBCRP to examine the ability to reverse drug resistance. Among the 8 inactive HABCRP cDNA clones tested, HABCRP cDNA clone 15 (HABCRP-15) that had an amino acid substitution from Leu to Pro at residue 554 reversed the drug resistance of MycBCRP. Login to comment
138 HABCRP-15 contained an amino acid substitution from Leu to Pro at residue 554 in the putative 5th transmembrane domain. Login to comment

PMID: 14576842 [PubMed] Doyle LA et al: "Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)."

No. Sentence Comment

82 Furthermore, a dominant-negative mutant of BCRP, with an L554P alteration in the fifth transmembrane domain, was found to inhibit BCRP function partially when cotransfected with BCRP. Login to comment
293 A mutant with an amino-acid change from Leu to Pro at residue 554 in the fifth transmembrane domain of BCRP resulted in the loss of transporter function, and was able to reverse partially the drug resistance of cotransfected wild-type BCRP. Login to comment

PMID: 15716365 [PubMed] Xia CQ et al: "Expression, localization, and functional characteristics of breast cancer resistance protein in Caco-2 cells."

No. Sentence Comment

135 The same group also demonstrates the necessity of homodimerization for the BCRP function when using a dominant-negative mutation of BCRP with a L554P alteration in the fifth transmembrane domain (Kage et al., 2002). Login to comment

PMID: 15769853 [PubMed] Henriksen U et al: "Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2."

No. Sentence Comment

226 Interestingly, a dominant-negative effect on drug sensitivity has been reported for ABCG2 (Kage et al., 2002) upon mutation of Leu554 situated in transmembrane segment 5 to a proline (L554P). Login to comment

PMID: 16108826 [PubMed] Sugimoto Y et al: "Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics."

No. Sentence Comment

53 Among the eight inactive mutant cDNAs, L554P-BCRP, with an amino acid change in TM5, was found to partially reverse drug resistance in MycBCRP-transfected cells (Fig. 1). Login to comment

PMID: 16146333 [PubMed] Mao Q et al: "Role of the breast cancer resistance protein (ABCG2) in drug transport."

No. Sentence Comment

171 In addition, a dominant-negative mutant of BCRP with amino acid change from Leu to Pro at position 554 in the TM5 segment was found to have partially reduced the ability to confer resistance to SN-38 and mitoxantrone when cotransfected with wild-type BCRP. Login to comment

PMID: 16618113 [PubMed] Polgar O et al: "Mutational studies of G553 in TM5 of ABCG2: a residue potentially involved in dimerization."

No. Sentence Comment

233 However, in the case of ABCG2, the inactive L554P mutant was reported to be able to partially reverse the drug resistance of PA317 cells cotransfected with the mutant and wild-type proteins, a result implying that residue 554 is critical for function, yet mutating this residue does not prevent dimerization. Login to comment

PMID: 17027309 [PubMed] Li YF et al: "Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study."

No. Sentence Comment

182 In sf9 cell, it is expressed on cell surface, but with no ATPase activity [56] L554P TM5 Lowered drug resistance [42] N557D,E TM5 Functional [21] S566Aa ECL (between TM5 and 6) Lowered drug resistance for the cell line [42] N596Q Between TM5 and 6 N-glycosylation site [65] Y605Ca Loop between TM5 and 6 Lowered drug resistance for the cell line [42] D620N Loop between TM5 and 6 SNP polymorphism [22] H630E,L TM6 Functional [21] A632Va TM Lowered drug resistance for the cell line [42] a Mutants not well characterized. Login to comment

PMID: 18249138 [PubMed] Hazai E et al: "Homology modeling of breast cancer resistance protein (ABCG2)."

No. Sentence Comment

245 However, in our model, R482 cannot form interaction with rhodamine, but L484 is in interacting distance Table 3 Mutations on BCRP and their effect on its function Mutation Effect/results Reference V12M Did not effect Hemato and MTX transport Tamura et al. (2006) G51C Did not effect Hemato and MTX transport Tamura et al. (2006) K86M Inactivates transporter (dominant negative effect on ATPase activity); alters subcellular distribution Henriksen et al. (2005a) K86M Transporter inactive, but still able to bind ATP Ozvegy et al. (2002) Q126stop Defective porphyrin transport Tamura et al. (2006) Q141K Did not effect Hemato and MTX transport Tamura et al. (2006) T153M Did not effect Hemato and MTX transport Tamura et al. (2006) Q166E Did not effect Hemato and MTX transport Tamura et al. (2006) I206L Did not effect Hemato and MTX transport Tamura et al. (2006) F208S Defective porphyrin transport Tamura et al. (2006) S248P Defective porphyrin transport Tamura et al. (2006) E334stop Defective porphyrin transport Tamura et al. (2006) F431L Effects MTX transport Tamura et al. (2006) S441N Defective porphyrin transport Tamura et al. (2006) E446-mutants No drug resistance Miwa et al. (2003) R482G, R482T Effects MTX transport Tamura et al. (2006) R482T Substrate drug transport and inhibitor efficiency is not mediated by changes in drug-binding Pozza et al. (2006) R482G, R482T Substitution influence the substrate specificity of the transporter Ozvegy et al. (2002) R482G, R482T Altered substrate specificity Honjo et al. (2001) R482G Methotrexate not transported Chen et al. (2003b) Mitomo et al. (2003) R482G Resistance to hydrophilic antifolates in vitro, G482-ABCG2 mutation confers high-level resistance to various hydrophilic antifolates Shafran et al., (2005) R482G Three distinct drug, binding sites Clark et al. (2006) R482G Altered substrate specificity, granulocyte maturation uneffected Ujhelly et al. (2003) R482 mutants Higher resistance to mitoxantrone and doxorubicin than wt Miwa et al. (2003) R482X Affects substrate transport and ATP hydrolysis but not substrate binding Ejendal et al. (2006) F489L Impaired porphyrin transport Tamura et al. (2006) G553L; G553E Impaired trafficing, expression, and N-linked glycosylation Polgar et al. (2006) L554P Dominant negative effect on drug sensitivity Kage et al. (2002) N557D Resistance to MTX, but decreased transport of SN-38; N557E no change in transport compared to wt Miwa et al. (2003) F571I Did not effect Hemato and MTX transport Tamura et al. (2006) N590Y Did not effect Hemato and MTX transport Tamura et al. (2006) C592A Impaired function and expression Henriksen et al. (2005b) C592A/C608A Restored plasma mb expression; MTX transport normal, BODIPY-prazosin impaired Henriksen et al. (2005b) C603A Disulfide bridge; no functional or membrane targeting change Henriksen et al. (2005b) C608A Impaired function and expression Henriksen et al. (2005b) D620N Did not effect Hemato and MTX transport Tamura et al. (2006) H630X No change in transport Miwa et al. (2003) Cand N-terminal truncated Impaired trafficing Takada et al. (2005) with the ligand. Login to comment

PMID: 22497316 [PubMed] Mo W et al: "Different roles of TM5, TM6, and ECL3 in the oligomerization and function of human ABCG2."

No. Sentence Comment

178 For example, it has been shown that the L554P mutation in TM5 reduces the drug resistance function of ABCG2.27 TM5 has also been found to contain a steroid binding element,28 further suggesting that TM5 may be important in substrate recognition and binding. Login to comment