Premium
Involvement of a guanine nucleotide‐exchange protein, ARF‐GEP 100 /BRAG2a, in the apoptotic cell death of monocytic phagocytes
Author(s) -
Someya Akimasa,
Moss Joel,
Nagaoka Isao
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0106059
Subject(s) - biology , apoptosis , microbiology and biotechnology , programmed cell death , fragmentation (computing) , u937 cell , annexin , guanine nucleotide exchange factor , death associated protein 6 , monocyte , transcription factor , signal transduction , nuclear protein , immunology , biochemistry , ecology , gene
We previous identified adenosine 5′‐diphosphate‐ribosylation factor (ARF)‐guanine nucleotide‐exchange protein, 100 kDa (GEP 100 ), as a novel GEP with a molecular size of ∼100 kDa, which preferentially activates ARF6. In this study, we examined the effect of ARF‐GEP 100 on monocytic cell apoptosis. Overexpression of ARF‐GEP 100 in PMA‐differentiated human monocyte‐macrophage‐like U937 cells and mouse macrophage RAW264.7 cells induced apoptotic cell death, which was detected by morphological changes (chromatin condensation, nucleus fragmentation, and shrinking of cytoplasm), annexin V‐staining, and TUNEL assay. It is interesting that a mutant lacking the Sec7 domain, which is responsible for ARF activation, was able to induce apoptosis of the target cells to the level of that of a wild‐type ARF‐GEP 100 . Furthermore, ARF‐GEP 100 ‐silencing experiments indicated that the TNF‐α‐induced apoptosis was significantly suppressed among ARF‐GEP 100 ‐depressed cells. These observations apparently suggest that ARF‐GEP 100 is involved in the induction of apoptosis in monocytic phagocytes, possibly independent of ARF activation.