The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors
| Autor: | Olga I. Lavrik, Tatyana A. Kurgina, Elizaveta E. Alemasova, Rashid O. Anarbaev, Konstantin N. Naumenko |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology poly(ADP-ribose) (PAR) Activator (genetics) Y-box binding protein 1 (YB-1) RNA PARP1 inhibitors olaparib Cofactor Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Histone PARP1 Oncology chemistry 030220 oncology & carcinogenesis Nucleic acid biology.protein poly(ADP-ribose) polymerase 1 (PARP1) DNA Polymerase Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.25158 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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