G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization.
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.
Brooks
William S
WS
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Banerjee
Sami
S
Crawford
David F
DF
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004249:DNA Damage / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000502:physiology; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D000097606:Exportin 1 Protein
D028884:Karyopherins; D019913:Nuclear Localization Signals; D018160:Receptors, Cytoplasmic and Nuclear; D044767:Ubiquitin-Protein Ligases; D000097606:Exportin 1 Protein; C518735:G2E3 protein, human