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http://purl.uniprot.org/citations/18288467http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18288467http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18288467http://www.w3.org/2000/01/rdf-schema#comment"We recently identified the Phafin protein family, whose members all contain an N-terminal PH domain (pleckstrin homology) and a C-terminal FYVE (Fab1, YGLO23, Vps27, and EEA1) domain. LAPF (lysosome-associated apoptosis-inducing protein containing PH and FYVE domains, also known as Phafin-1), as one representative member of this new family, has been shown to be able to initiate caspase-independent apoptosis through lysosomal-mitochondrial apoptotic pathway. Here, we describe the cloning and functional characterization of another Phafin member, EAPF (endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains)/Phafin-2. Overexpression of EAPF/Phafin-2 enhances the sensitivity of L929 and MCF-7 cells to TNF-alpha-induced apoptosis, concomitant with its partial translocation to endoplasmic reticulum (ER). Both the PH and the FYVE domains contribute to the ER translocation of EAPF/Phafin-2 as well as EAPF/Phafin-2-enhanced apoptosis. Knockdown of mouse and human EAPF/Phafin-2 expression protects L929 cells and MCF-7 cells from TNF-alpha-induced apoptosis, respectively. We demonstrate that EAPF/Phafin-2 induces a much sharper and more rapid Ca2+ influx triggered by TNF-alpha and Ca2+ release ER contributes to the enhancement of EAPF/Phafin-2 in TNF-induced apoptosis. EAPF/Phafin-2 increases the activity of caspase 12, suggesting that EAPF/Phafin-2 is involved in ER-related apoptotic pathway. Overexpression of EAPF/Phafin-2 also enhances TNF-alpha-induced activity of caspase 3 (but not caspase 8 or 9), and promotes TNF-alpha-triggered mitochondrial membrane permeabilization (MMP) in L929 cells, including dissipation of mitochondrial membrane potential and release of AIF. Besides, EAPF/Phafin-2 also suppresses the unfolded protein response by inhibiting phosphorylation of eIF2alpha. Therefore, our results demonstrate that EAPF/Phafin-2 facilitates TNF-alpha-induced cellular apoptosis through an ER-mitochondrial apoptotic pathway, which may improve our understanding of drug-induced cancer cell death and cancer chemotherapy."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.org/dc/terms/identifier"doi:10.1007/s00109-007-0298-7"xsd:string
http://purl.uniprot.org/citations/18288467http://purl.org/dc/terms/identifier"doi:10.1007/s00109-007-0298-7"xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Chen W."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Chen W."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Cao X."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Cao X."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Li C."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Li C."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Liu Q."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Liu Q."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Li N."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Li N."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Yu Y."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/author"Yu Y."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/name"J. Mol. Med."xsd:string
http://purl.uniprot.org/citations/18288467http://purl.uniprot.org/core/name"J. Mol. Med."xsd:string
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