ADP ribosylation by PARP-1 suppresses HOXB7 transcriptional activity

Xinyan Wu, Stephan Ellmann, Ethel Rubin, Minchan Gil, Kideok Jin, Liangfeng Han, Hexin Chen, Erika M. Kwon, Jianhui Guo, Hyo Chol Ha, Saraswati Sukumar

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Interactions with cofactors regulate transcriptional activity and also help HOX proteins to achieve the specificity required for transcriptional regulation of target genes. In this study, we describe a novel protein/protein interaction of HOXB7 with poly (ADP-ribose) polymerase-1 (PARP-1) that involves the homeodomain of HOXB7 and the first zinc finger domain of PARP-1. Upon binding to PARP-1, HOXB7 undergoes poly(ADP-ribosyl)altion resulting in a reduction of its transcriptional activity. Since aspartic acid and glutamic acid residues are acceptors of the ADP ribose moiety transferred by PARP-1, deletion of the evolutionarily conserved C-terminal Glu-rich tail of HOXB7 dramatically attenuates ADP-ribosylation of HOXB7 by PARP-1. Further, a mutant of HOXB7 without the Glu-rich tail loses the ability to be negatively regulated by PARP-1 and becomes transcriptionally more active in luciferase reporter assays. Since the homeodomain is highly conserved among HOX proteins, five other HOX proteins were tested. All six showed interaction with, and were poly(ADP-ribosyl)ated by PARP-1. However, among them, this modification altered the DNA binding activity of only HOXA7 and HOXB7. In summary, this study identifies a new interacting partner of HOX proteins. More importantly, this study reveals a novel mechanism whereby polyADP-ribosylation regulates transcriptional activities of HOX proteins such as HOXB7 and HOXA7.

Original languageEnglish (US)
Article numbere40644
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 23 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Wu, X., Ellmann, S., Rubin, E., Gil, M., Jin, K., Han, L., Chen, H., Kwon, E. M., Guo, J., Ha, H. C., & Sukumar, S. (2012). ADP ribosylation by PARP-1 suppresses HOXB7 transcriptional activity. PloS one, 7(7), [e40644]. https://doi.org/10.1371/journal.pone.0040644