Oligomerization domain of the multidrug resistance-associated transporter ABCG2 and its dominant inhibitory activity

Junkang Xu, Hui Peng, Qun Chen, Yang Liu, Zizheng Dong, Jian-Ting Zhang

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Overexpression of human ATP-binding cassette transporter ABCG2 in cancer cells causes multidrug resistance by effluxing anticancer drugs. ABCG2 is considered as a half transporter and is thought to function as a homodimer. However, recent evidence suggests that it may exist as a higher form of oligomer consisting of 12 summits. In this study, we mapped the oligomerization domain of human ABCG2 to its transmembrane domain consisting of TM5-loop-TM6. This oligomerization domain, when expressed alone in HEK293 cells, also forms a homododecamer. Furthermore, this domain has activity that inhibits drug efflux and resistance function of the full-length ABCG2 likely by disrupting the formation of the homo-oligomeric full-length ABCG2. These findings suggest that human ABCG2 may exist and work as a homo-oligomer by interactions located in TM5-loop-TM6, and that ABCG2 oligomerization may be used as a target for therapeutic development to circumvent ABCG2-mediated drug resistance in cancer treatment.

Original languageEnglish
Pages (from-to)4373-4381
Number of pages9
JournalCancer Research
Volume67
Issue number9
DOIs
StatePublished - May 1 2007

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Multiple Drug Resistance
Drug Resistance
ATP-Binding Cassette Transporters
HEK293 Cells
Neoplasms
Pharmaceutical Preparations
ATP Binding Cassette Transporter, Sub-Family G, Member 2
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Oligomerization domain of the multidrug resistance-associated transporter ABCG2 and its dominant inhibitory activity. / Xu, Junkang; Peng, Hui; Chen, Qun; Liu, Yang; Dong, Zizheng; Zhang, Jian-Ting.

In: Cancer Research, Vol. 67, No. 9, 01.05.2007, p. 4373-4381.

Research output: Contribution to journalArticle

Xu, Junkang ; Peng, Hui ; Chen, Qun ; Liu, Yang ; Dong, Zizheng ; Zhang, Jian-Ting. / Oligomerization domain of the multidrug resistance-associated transporter ABCG2 and its dominant inhibitory activity. In: Cancer Research. 2007 ; Vol. 67, No. 9. pp. 4373-4381.
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