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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2005-5-17
pubmed:abstractText
In this study, we cloned and characterized a human gene homologous to the apoptosis-inducing factor (AIF), which is named AIF-like (AIFL). Human AIFL has 598 amino acids, with a characteristic Rieske domain and a pyridine nucleotide-disulfide oxidoreductase domain (Pyr_redox). AIFL shares 35% homology with AIF, mainly in the Pyr_redox domain. Reverse transcriptase-PCR analysis showed the expression of AIFL mRNA in all tissues tested, i.e. brain, colon, heart, kidney, liver, lung, muscle, ovary, pancreas, placenta, small intestine, and testis. We developed antibodies against human AIFL using fusion proteins as antigens. The antibodies specifically recognized the antigen and heterologously expressed AIFL proteins. The expression of AIFL proteins in human tissues was also ubiquitous, demonstrated by immunohistochemistry in tissue array slides. Subcellular fractionation and immunofluorescence staining studies revealed that AIFL is predominantly localized to the mitochondria. Similar to AIF, overexpression of AIFL induced apoptosis, as shown by increased cytoplasmic nucleosomes and subdiploid cell populations in AIFL-transfected cells. The segment 1-190 containing the Rieske domain induced apoptosis, whereas the segment containing the Pyr_redox domain did not contribute to the pro-apoptotic function. The mitochondrial membrane potential of cells transfected with AIFL was significantly more depolarized than that of the control. AIFL transfection-induced cytochrome c release and cleavage of caspase 3. Furthermore, the pan-caspase inhibitor Z-VAD-fmk inhibited AIFL induced apoptosis. In summary, AIFL induces apoptosis in a caspase-dependent manner when heterologously expressed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19673-81
pubmed:dateRevised
2011-5-5
pubmed:meshHeading
pubmed-meshheading:15764604-Amino Acid Sequence, pubmed-meshheading:15764604-Apoptosis, pubmed-meshheading:15764604-Apoptosis Inducing Factor, pubmed-meshheading:15764604-Cloning, Molecular, pubmed-meshheading:15764604-Female, pubmed-meshheading:15764604-Flavoproteins, pubmed-meshheading:15764604-Gene Expression, pubmed-meshheading:15764604-Humans, pubmed-meshheading:15764604-Male, pubmed-meshheading:15764604-Membrane Potentials, pubmed-meshheading:15764604-Membrane Proteins, pubmed-meshheading:15764604-Mitochondria, pubmed-meshheading:15764604-Molecular Sequence Data, pubmed-meshheading:15764604-Pregnancy, pubmed-meshheading:15764604-Protein Structure, Tertiary, pubmed-meshheading:15764604-RNA, Messenger, pubmed-meshheading:15764604-Recombinant Proteins, pubmed-meshheading:15764604-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15764604-Sequence Homology, Amino Acid, pubmed-meshheading:15764604-Tissue Distribution, pubmed-meshheading:15764604-Transfection
pubmed:year
2005
pubmed:articleTitle
Molecular cloning and characterization of a human AIF-like gene with ability to induce apoptosis.
pubmed:affiliation
Indiana University School of Optometry, Bloomington, 47405, USA.
pubmed:publicationType
Journal Article