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Apoptosis‐inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g)
Author(s) -
Kim Jong-Tae,
Kim Kwang Dong,
Song Eun Young,
Lee Hee Gu,
Kim Jae Wha,
Kim Jung Woo,
Chae Suhn-Kee,
Kim Eunhee,
Lee Myeong-Sok,
Yang Young,
Lim Jong-Seok
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.10.049
Subject(s) - apoptosis inducing factor , mitochondrial intermembrane space , microbiology and biotechnology , protein subunit , biology , transcription factor , immunoprecipitation , eif4a1 , initiation factor , translation (biology) , caspase , chemistry , apoptosis , biochemistry , programmed cell death , messenger rna , gene , bacterial outer membrane , escherichia coli
Apoptosis‐inducing factor (AIF) is a ubiquitous FAD‐binding flavoprotein comprised of 613 amino acids and plays an important role in caspase‐independent apoptosis. During apoptotic induction, AIF is translocated from the mitochondrial intermembrane space to the nucleus, where it interacts with DNA and activates a nuclear endonuclease. By performing a yeast two‐hybrid screen with mature AIF, we have isolated the eukaryotic translation initiation factor 3 subunit p44 (eIF3g). Our deletion mutant analysis revealed that the eIF3g N‐terminus interacts with the C‐terminal region of AIF. The direct interaction between AIF and eIF3g was confirmed in a GST pull‐down assay and also verified by the results of co‐immunoprecipitation and confocal microscopy studies. Using an in vitro TNT coupled transcription–translation system, we found that mature AIF could inhibit newly‐translated protein synthesis and this inhibition was significantly blocked by eIF3g competitively. These results were also confirmed in cells. In addition, mature AIF overexpression specifically resulted in the activation of caspase‐7, thereby amplifying the inhibition of protein synthesis including eIF3g cleavage. Our data suggest that eIF3g is one of the cytosolic targets that interacts with mature AIF, and provide insight into the AIF's cellular functions of the inhibition of protein synthesis during apoptosis.