Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis

Youyun Yang, Zhaomin Li, Wei Mo, Raghuram Ambadipudi, Randy J. Arnold, Petra Hrncirova, Milos V. Novotny, Elias Georges, Jian-Ting Zhang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Human ABCC1 is a member of the ATP-binding cassette (ABC) transporter superfamily, and its overexpression has been shown to cause multidrug resistance by active efflux of a wide variety of anticancer drugs. ABCC1 has been shown to exist and possibly function as a homodimer. However, a possible heterocomplex involving ABCC1 has been indicated. In this study, we performed an interactive proteomics study to examine proteins that bind to and form heterocomplexes with ABCC1 using coimmunoprecipitation and tandem mass spectrometry (MS/MS) analyses. We found that ATP synthase α binds to ABCC1 in plasma membranes with a ratio of 2:1. The ATP synthase α binding site in ABCC1 is located in the linker domain at the carboxyl core of ABCC1, and phosphorylation of the linker domain at the protein kinase A site enhances ATP synthase α binding. The interaction between ABCC1 and ATP synthase α in a heterocomplex may indicate a novel function of ABCC1 in regulating extracellular ATP level and purinergic signaling cascade.

Original languageEnglish
Pages (from-to)1364-1372
Number of pages9
JournalJournal of Proteome Research
Volume11
Issue number2
DOIs
StatePublished - Feb 3 2012

Fingerprint

Proteomics
Adenosine Triphosphate
Phosphorylation
ATP-Binding Cassette Transporters
Multiple Drug Resistance
Cell membranes
Tandem Mass Spectrometry
Cyclic AMP-Dependent Protein Kinases
Mass spectrometry
Binding Sites
Cell Membrane
Pharmaceutical Preparations
Proteins

Keywords

  • ABC transporter
  • ABCC1
  • ATP synthase
  • drug resistance
  • MRP1
  • oligomers

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Yang, Y., Li, Z., Mo, W., Ambadipudi, R., Arnold, R. J., Hrncirova, P., ... Zhang, J-T. (2012). Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis. Journal of Proteome Research, 11(2), 1364-1372. https://doi.org/10.1021/pr201003g

Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis. / Yang, Youyun; Li, Zhaomin; Mo, Wei; Ambadipudi, Raghuram; Arnold, Randy J.; Hrncirova, Petra; Novotny, Milos V.; Georges, Elias; Zhang, Jian-Ting.

In: Journal of Proteome Research, Vol. 11, No. 2, 03.02.2012, p. 1364-1372.

Research output: Contribution to journalArticle

Yang, Y, Li, Z, Mo, W, Ambadipudi, R, Arnold, RJ, Hrncirova, P, Novotny, MV, Georges, E & Zhang, J-T 2012, 'Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis', Journal of Proteome Research, vol. 11, no. 2, pp. 1364-1372. https://doi.org/10.1021/pr201003g
Yang, Youyun ; Li, Zhaomin ; Mo, Wei ; Ambadipudi, Raghuram ; Arnold, Randy J. ; Hrncirova, Petra ; Novotny, Milos V. ; Georges, Elias ; Zhang, Jian-Ting. / Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis. In: Journal of Proteome Research. 2012 ; Vol. 11, No. 2. pp. 1364-1372.
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