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Identification of a functional nuclear export sequence in the apoptosis‐modulating protein Aven
Author(s) -
Kuhn Helena M,
Irusta Pablo M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a992-a
Subject(s) - biology , nuclear export signal , cytoplasm , mutant , nuclear protein , nuclear localization sequence , apoptosis , microbiology and biotechnology , nls , cell nucleus , peptide sequence , intracellular , genetics , gene , transcription factor
Aven is a recently identified protein that interacts with Bcl‐2 family members and affects cell fate by modulating apoptosis. Inside cells, Aven is predominantly found in the cytoplasm, although a small proportion of the protein localizes to the nucleus. The roles played by the nuclear versus cytoplasmic pools of Aven in the apoptosis‐modulating functions displayed by the protein have not been elucidated. In search of protein regions governing the intracellular trafficking of Aven, we analyzed its amino acid sequence and identified two leucine‐rich domains resembling canonical nuclear export signals (NES). These two putative NES sequences are located between residues 190–196 and residues 286–292, respectively. We generated mutant Aven proteins carrying leucine to alanine substitutions at positions predicted to disrupt the putative export signals and analyzed the effects of these mutations on the localization and apoptosis‐modulating functions of Aven. Our results demonstrated that disruption of the second putative NES sequence of Aven (residues 286–292) leads to a significant accumulation of the protein in the nuclear compartment, indicating that this region functions as a bona fide nuclear export signal. Furthermore, Aven proteins with disrupted NES sequences displayed altered apoptosis‐modulating functions.