title: ZFAT is a critical molecule for cell survival in mouse embryonic fibroblasts.
abstract: ZFAT was originally identified as an immune-related transcriptional regulator containing 18 C2H2-type zinc-finger domains and one AT-hook. ZFAT is highly conserved among species and functions as an anti-apoptotic molecule in the lymphoblastic leukemia cell line, MOLT-4. We recently demonstrated that ZFAT is an essential molecule for hematopoietic differentiation in blood islands through the direct regulation of particular transcriptional factors, including Tal1, for endothelial cell assembly, and for the branch point formation of capillary-like structures. However, the molecular mechanisms underlying the anti-apoptotic function of ZFAT remain unknown. Here, we report that ZFAT knockdown by small interfering RNA induced apoptosis in mouse embryonic fibroblasts (MEFs). This response had been similarly observed for MOLT-4 cells. To explore the molecular mechanisms for ZFAT in anti-apoptotic function in both MEFs and MOLT-4 cells, microarray expression analysis and quantitative RT-PCR were done. Of interest was that Bcl-2 and Il6st were identified as commonly down-regulated genes by the depletion of ZFAT for both MEFs and MOLT-4 cells. These results suggest that ZFAT is a critical molecule for cell survival in MEFs and MOLT-4 cells at least in part through the regulation of the apoptosis involved in the BCL-2- and IL6st-mediated pathways. Further elucidation of the molecular functions for ZFAT might shed light on the cellular programs in the mesoderm-derived cells.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Doi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Midori
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takashima
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C494200:Il6st protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D014157:Transcription Factors; C529571:ZFAT protein, mouse; D050822:Cytokine Receptor gp130