The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors
- PMID: 29805738
- PMCID: PMC5955111
- DOI: 10.18632/oncotarget.25158
The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors
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).
Conflict of interest statement
CONFLICTS OF INTEREST The authors declare that there is no conflict of interest in this work.
Figures









References
-
- Sánchez-Pérez I. DNA repair inhibitors in cancer treatment. Clin Transl Oncol. 2006;8:642–46. https://doi.org/10.1007/s12094-006-0034-8. - DOI - PubMed
-
- Davar D, Beumer JH, Hamieh L, Tawbi H. Role of PARP inhibitors in cancer biology and therapy. Curr Med Chem. 2012;19:3907–21. https://doi.org/10.2174/092986712802002464. - DOI - PMC - PubMed
-
- Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD, Karch KR, McCauley M, Steffen JD, Black BE, Pascal JM. PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain. Mol Cell. 2015;60:755–68. https://doi.org/10.1016/j.molcel.2015.10.013. - DOI - PMC - PubMed
-
- D’Amours D, Desnoyers S, D’Silva I, Poirier GG. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999;342:249–68. https://doi.org/10.1042/bj3420249. - DOI - PMC - PubMed
-
- Teloni F, Altmeyer M. Readers of poly(ADP-ribose): designed to be fit for purpose. Nucleic Acids Res. 2016;44:993–1006. https://doi.org/10.1093/nar/gkv1383. - DOI - PMC - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous