The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors

Elizaveta E. Alemasova, Konstantin N. Naumenko, Tatyana A. Kurgina, Rashid O. Anarbaev, Olga I. Lavrik

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Y-box-binding protein 1 (YB-1) is a multifunctional cellular factor overexpressed in tumors resistant to chemotherapy. An intrinsically disordered structure together with a high positive charge peculiar to YB-1 allows this protein to function in almost all cellular events related to nucleic acids including RNA, DNA and poly(ADP-ribose) (PAR). In the present study we show that YB-1 acts as a potent poly(ADP-ribose) polymerase 1 (PARP1) cofactor that can reduce the efficiency of PARP1 inhibitors. Similarly to that of histones or polyamines, stimulatory effect of YB-1 on the activity of PARP1 was significantly higher than the activator potential of Mg2+ and was independent of the presence of EDTA. The C-terminal domain of YB-1 proved to be indispensable for PARP1 stimulation. We also found that functional interactions of YB-1 and PARP1 can be mediated and regulated by poly(ADP-ribose).

Original languageEnglish
Pages (from-to)23349-23365
Number of pages17
JournalOncotarget
Volume9
Issue number34
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Olaparib
  • PARP1 inhibitors
  • Poly(ADP-ribose) (PAR)
  • Poly(ADP-ribose) polymerase 1 (PARP1)
  • Y-box binding protein 1 (YB-1)

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