G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization

William S. Brooks, Sami Banerjee, David F. Crawford

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

G2E3 was originally described as a G2/M-specific gene with DNA damage responsive expression. The presence of a conserved HECT domain within the carboxy-terminus of the protein indicated that it likely functions as a ubiquitin ligase or E3. Although HECT domains are known to function in this capacity for many proteins, we demonstrate that a portion of the HECT domain from G2E3 plays an important role in the dynamic subcellular localization of the protein. We have shown that G2E3 is a nucleo-cytoplasmic shuttling protein with nuclear export mediated by a novel nuclear export domain that functions independently of CRM1. In full-length G2E3, a separate region of the HECT domain suppresses the function of the NES. Additionally, G2E3 contains a nucleolar localization signal (NoLS) in its amino terminus. Localization of G2E3 to the nucleolus is a dynamic process, and the protein delocalizes from the nucleolus rapidly after DNA damage. Cell cycle phase-specific expression and highly regulated subcellular localization of G2E3 suggest a possible role in cell cycle regulation and the cellular response to DNA damage.

Original languageEnglish (US)
Pages (from-to)665-676
Number of pages12
JournalExperimental Cell Research
Volume313
Issue number4
DOIs
StatePublished - Feb 15 2007
Externally publishedYes

Keywords

  • CRM1
  • DNA damage
  • HECT
  • Leptomycin B
  • Nuclear export
  • Nucleolus
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Cell Biology

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