Open Access

ZFAT is a critical molecule for cell survival in mouse embryonic fibroblasts

  • Keiko Doi1, 2,
  • Takahiro Fujimoto1, 2,
  • Midori Koyanagi1, 2,
  • Toshiyuki Tsunoda1, 2,
  • Yoko Tanaka1, 2,
  • Yasuhiro Yoshida1,
  • Yasuo Takashima2,
  • Masahide Kuroki2,
  • Takehiko Sasazuki3 and
  • Senji Shirasawa1, 2Email author
Cellular & Molecular Biology LettersAn International Journal201016:41

DOI: 10.2478/s11658-010-0041-1

Received: 13 September 2010

Accepted: 8 December 2010

Published: 27 December 2010

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.

Key words

ZFAT Transcription factor MEFs Apoptosis Gene expression

Advertisement