RNF2 interacts with the linker region of the human P-glycoprotein

  • Authors:
    • Prema S. Rao
    • Kavita B. Mallya
    • Kalkunte S. Srivenugopal
    • K. C. Balaji
    • U. Subrahmanyeswara Rao
  • View Affiliations

  • Published online on: December 1, 2006     https://doi.org/10.3892/ijo.29.6.1413
  • Pages: 1413-1419
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Abstract

The human P-glycoprotein (Pgp) is a drug-efflux pump responsible for innate or acquired multidrug resistance in many cancers. Pgp contains a unique ≈75 amino acid long linker region in its middle, which is critically important for its drug transport and ATPase functions. To identify cellular proteins that bind to this linker region and modulate Pgp function, a yeast two-hybrid analysis was carried out. This procedure identified RNF2 (RING finger protein 2), an E3 ubiquitin ligase, as a prominent Pgp-interacting protein. Co-expression of RNF2 with Pgp in Sf9 insect cells resulted in decreased ATPase activity and proteolytic protection of the transporter protein. Immunoprecipitation experiments confirmed the physical interaction between these two proteins. Confocal microscopy showed the presence of RNF2 in the cytoplasm of the Pgp-negative, drug-sensitive MCF-7 breast cancer cells. However, it was undetectable in the Pgp-positive and drug-resistant MCF-7 cells. We suggest that RNF2 regulates the cellular abundance of Pgp, and plays a key role in the development of cancer drug resistance through its own down-regulation.

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December 2006
Volume 29 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Rao PS, Mallya KB, Srivenugopal KS, Balaji KC and Rao US: RNF2 interacts with the linker region of the human P-glycoprotein. Int J Oncol 29: 1413-1419, 2006
APA
Rao, P.S., Mallya, K.B., Srivenugopal, K.S., Balaji, K.C., & Rao, U.S. (2006). RNF2 interacts with the linker region of the human P-glycoprotein. International Journal of Oncology, 29, 1413-1419. https://doi.org/10.3892/ijo.29.6.1413
MLA
Rao, P. S., Mallya, K. B., Srivenugopal, K. S., Balaji, K. C., Rao, U. S."RNF2 interacts with the linker region of the human P-glycoprotein". International Journal of Oncology 29.6 (2006): 1413-1419.
Chicago
Rao, P. S., Mallya, K. B., Srivenugopal, K. S., Balaji, K. C., Rao, U. S."RNF2 interacts with the linker region of the human P-glycoprotein". International Journal of Oncology 29, no. 6 (2006): 1413-1419. https://doi.org/10.3892/ijo.29.6.1413