![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan
The ATP-binding cassette (ABC) transporter ABCG2 has been implicated to play a significant role in the response of patients to medication and/or the risk of diseases. To clarify the possible physiological or pathological relevance of ABCG2 polymorphisms, we have functionally validated single nucleotide polymorphisms (SNP) of ABCG2. In the present study, based on the currently available data on SNPs and acquired mutations, we have created a total of 18 variant forms of ABCG2 (V12M, G51C, Q126stop, Q141K, T153M, Q166E, I206L, F208S, S248P, E334stop, F431L, S441N, R482G, R482T, F489L, F571I, N590Y, and D620N) by site-directed mutagenesis and expressed them in insect cells. Because porphyrins are considered to be endogenous substrates for ABCG2, we have investigated the porphyrin transport activity of those variant forms in vitro. We herein provide evidence that the variants Q126stop, F208S, S248P, E334stop, and S441N are defective in porphyrin transport, whereas F489L exhibited impaired transport, approximately 10% of the activity observed for the wild type. Furthermore, Flp-In-293 cells expressing those variants were photosensitive. Thus, among those genetic polymorphisms of ABCG2, at least the hitherto validated alleles of Q126stop, S441N, and F489L are suggested to be of clinical importance related to the potential risk of porphyria.
Address correspondence to: Dr. Toshihisa Ishikawa, Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-60 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan. E-mail: tishikaw{at}bio.titech.ac.jp
This article has been cited by other articles:
|
|
 |
|
  O. Protchenko, M. Shakoury-Elizeh, P. Keane, J. Storey, R. Androphy, and C. C. Philpott Role of PUG1 in Inducible Porphyrin and Heme Transport in Saccharomyces cerevisiae Eukaryot. Cell, May 1, 2008; 7(5): 859 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Poonkuzhali, J. Lamba, S. Strom, A. Sparreboom, K. Thummel, P. Watkins, and E. Schuetz Association of Breast Cancer Resistance Protein/ABCG2 Phenotypes and Novel Promoter and Intron 1 Single Nucleotide Polymorphisms Drug Metab. Dispos., April 1, 2008; 36(4): 780 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wakabayashi, H. Nakagawa, A. Tamura, S. Koshiba, K. Hoshijima, M. Komada, and T. Ishikawa Intramolecular Disulfide Bond Is a Critical Check Point Determining Degradative Fates of ATP-binding Cassette (ABC) Transporter ABCG2 Protein J. Biol. Chem., September 21, 2007; 282(38): 27841 - 27846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Jonker, S. Musters, M. L. H. Vlaming, T. Plosch, K. E. R. Gooijert, M. J. Hillebrand, H. Rosing, J. H. Beijnen, H. J. Verkade, and A. H. Schinkel Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2204 - C2212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Lee, H.-E. Jeong, J.-M. Yi, H.-J. Jung, J.-E. Jang, E.-Y. Kim, S.-J. Lee, and J.-G. Shin Identification and Functional Assessment of BCRP Polymorphisms in a Korean Population Drug Metab. Dispos., April 1, 2007; 35(4): 623 - 632. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
