Poly(ADP-ribosyl)ation is recognized by ECT2 during mitosis

Cell Cycle. 2014;13(18):2944-51. doi: 10.4161/15384101.2014.947197.

Abstract

Poly(ADP-ribosyl)ation is an unique posttranslational modification and required for spindle assembly and function during mitosis. However, the molecular mechanism of poly(ADP-ribose) (PAR) in mitosis remains elusive. Here, we show the evidence that PAR is recognized by ECT2, a key guanine nucleotide exchange factor in mitosis. The BRCT domain of ECT2 directly binds to PAR both in vitro and in vivo. We further found that α-tubulin is PARylated during mitosis. PARylation of α-tubulin is recognized by ECT2 and recruits ECT2 to mitotic spindle for completing mitosis. Taken together, our study reveals a novel mechanism by which PAR regulates mitosis.

Keywords: Abbreviations: PAR; BRCA1 C Terminus; CHFR; BRCA1-associated RING domain protein 1; BRCT; BRCT domain; Breast Cancer Gene 1; BARD1; Dbl homology; PH; ECT2; Ethylenediaminetetraacetic acid; GST; PAR; PAR binding; Poly(ADP-ribose) polymerase 1; RhoGEF; Rho guanine nucleotide exchange factor; TBST; Tris-Buffered Saline and Tween 20.; checkpoint with forkhead-associated and ring finger; DH; epithelial cell transforming sequence 2 oncogene; BRCA1; glutatione S-transferase; PARG; mitosis; pleckstrin homology; PBC; poly(ADP-ribose) glycohydrolase gene; PARP-1; poly(ADP-ribose); PARylation; poly(ADP-ribosyl)ation; ECT2; polybasic cluster; EDTA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cytokinesis
  • HeLa Cells
  • Humans
  • Mitosis*
  • Models, Biological
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / metabolism*
  • Spindle Apparatus / metabolism
  • Tankyrases / metabolism
  • Tubulin / metabolism

Substances

  • ECT2 protein, human
  • Proto-Oncogene Proteins
  • Tubulin
  • Poly Adenosine Diphosphate Ribose
  • Tankyrases
  • TNKS protein, human