title: TIP47 confers resistance to taxol-induced cell death by preventing the nuclear translocation of AIF and Endonuclease G.
abstract: Tail-interacting protein (TIP47, also named PP17) has been implicated in lipid droplet metabolism and in the development of late endosomes, to date however, no data about its possible role in regulating cell death processes has been available. Here, we provide evidence for the role of TIP47 in the regulation of mitochondrial membrane stability and cell death. Overexpression of TIP47 protected NIH3T3 cells from taxol-induced cell death, while suppression of TIP47 by siRNA facilitated cell death. TIP47, but not its truncated form, t-TIP47, decreased taxol-induced cell death as determined by propidium iodide and fluorescent Annexin V staining. Recombinant TIP47, but not t-TIP47, partially prevented taxol-induced depolarization of mitochondria in vitro. Overexpression of TIP47, but not its truncated form, prevented the taxol-induced nuclear and cytoplasmic translocation of AIF and Endonuclease G, as well as the taxol-induced depolarization of mitochondria in NIH3T3 cells. Furthermore, overexpression of TIP47 facilitated Bcl-2 expression and suppressed Bax expression in taxol-treated cells. These data show that besides its previously known functions, TIP47 is involved in the regulation of mitochondria-related cell death by directly stabilizing the mitochondrial membrane system and by favorably affecting the expression of Bcl-2 homologues. Since TIP47 is overexpressed in certain tumors, it is possible that TIP47 contributes to the development of cytostatic resistance.
authors: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors: Eniko
authors: E
authors: Hocsak
authors: Boglarka
authors: B
authors: Racz
authors: Aliz
authors: A
authors: Szabo
authors: Eva
authors: E
authors: Pozsgai
authors: Andras
authors: A
authors: Szigeti
authors: Edit
authors: E
authors: Szigeti
authors: Ferenc
authors: F
authors: Gallyas
authors: Balazs
authors: B
authors: Sumegi
authors: Szaniszlo
authors: S
authors: Javor
authors: Szabolcs
authors: S
authors: Bellyei
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D015398:Signal Transduction; D014162:Transfection; D033921:Vesicular Transport Proteins
chemical_list: D051033:Apoptosis Inducing Factor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; C523440:Plin3 protein, mouse; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D017239:Paclitaxel