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

// Elizaveta E. Alemasova 1 , Konstantin N. Naumenko 1, 2 , Tatyana A. Kurgina 1, 2 , Rashid O. Anarbaev 1, 2 and Olga I. Lavrik 1, 2 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 Correspondence to: Olga I. Lavrik, email: lavrik@niboch.nsc.ru Keywords: Y-box binding protein 1 (YB-1); poly(ADP-ribose) polymerase 1 (PARP1); poly(ADP-ribose) (PAR); PARP1 inhibitors; olaparib Abbreviations: YB-1: Y-box binding protein 1; PARP1: poly(ADP-ribose) polymerase 1; PAR: poly(ADP-ribose) Received: August 15, 2017      Accepted: April 02, 2018      Published: May 04, 2018 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 Mg 2+ 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).