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

52 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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