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

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Research Papers:

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 and Olga I. Lavrik _

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Oncotarget. 2018; 9:23349-23365. https://doi.org/10.18632/oncotarget.25158

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Abstract

Elizaveta E. Alemasova1, Konstantin N. Naumenko1,2, Tatyana A. Kurgina1,2, Rashid O. Anarbaev1,2 and Olga I. Lavrik1,2

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

2Novosibirsk State University, Novosibirsk, 630090, Russia

Correspondence to:

Olga I. Lavrik, email: [email protected]

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 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).

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Research Papers:

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

Abstract