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

doi:10.18632/oncotarget.25158

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

Oncotarget. 2018 May 4;9(34):23349-23365. doi: 10.18632/oncotarget.25158.

Authors

Elizaveta E Alemasova¹, Konstantin N Naumenko^{1

2}, Tatyana A Kurgina^{1

2}, Rashid O Anarbaev^{1

2}, Olga I Lavrik^{1

2}

Affiliations

¹ Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russia.
² Novosibirsk State University, Novosibirsk, 630090, Russia.

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).

Keywords: PARP1 inhibitors; Y-box binding protein 1 (YB-1); olaparib; poly(ADP-ribose) (PAR); poly(ADP-ribose) polymerase 1 (PARP1).