Biomedical subjects

Tadayuki Akagi

Publications and source records attributed to Tadayuki Akagi.

3 recordsLinked to original sources

PubMed2006

GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal. In this study, we searched for molecules downstream of STAT3 in ES cells. Using DNA chip analysis, we obtained GA-repeat binding protein (GABP) alpha. Expression of GABPalpha was restricted to undifferentiated ES cells and controlled by STAT3. We found that the expression level of Oct-3/4 is reduced by knockdown of GABPalpha. On the other hand, GABPalpha-overexpressing ES cells maintained the expression level of Oct-3/4 even in the absence of LIF. Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup-tf1, and GCNF was stimulated by GABPalpha knockdown. These data suggest that GABPalpha upregulates the expression of Oct-3/4 via downregulation of Oct-3/4 repressors.

Animals↗

PubMed2005

Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor STAT3 is essential for the self-renewal of ES cells. In this study, we searched for downstream molecules of STAT3 in ES cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The expression of Zfp-57 was restricted to undifferentiated ES cells and activation of STAT3 led to expression of Zfp-57. We also found that forced expression of a dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down-regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross phenotypical defects, including expression of undifferentiated-state-specific genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct-3/4 in ES cells, although dispensable for their self-renewal.

Animals↗

PubMed2001

Identification of the nucleocytoplasmic shuttling sequence of heterogeneous nuclear ribonucleoprotein D-like protein JKTBP and its interaction with mRNA.

JKTBP proteins are related to a family of heterogeneous nuclear ribonucleoproteins (hnRNPs) that function in mRNA biogenesis and mRNA metabolism. JKTBP proteins constituted of isoforms 1, 2, and 1Delta6 are localized in the nucleus. We show that the dominant form JKTBP1 shuttles between the nucleus and the cytoplasm and interacts with mRNA. Immunofluorescence microscopy and immunoblotting of the subcellular fractions and overexpression of JKTBP tagged with green fluorescent protein indicated that JKTBP1 and JKTBP1Delta6, but not JKTBP2, accumulate in the cytoplasm upon polymerase II transcription inhibition. After release from inhibition, the return of accumulated cytoplasmic JKTBP to the nucleus was temperature-dependent. In heterokaryons, green fluorescent protein-tagged JKTBP1 and JKTBP1Delta6 migrated from the HeLa nucleus to the mouse nucleus, but JKTBP2 did not. Using various JKTBP deletion mutants, the 25-residue C-terminal tail was identified as a shuttling sequence like M9. It is conserved in the C-terminal tails of hnRNP D/AUF1 and type A/B hnRNP/ABBP-1. Analysis of its sequence-specific interacting protein indicated that JKTBP nuclear import is mediated by the receptor transportin 1/karyopherin beta2. UV cross-linking revealed the increased occurrence of JKTBP1 directly interacting with poly(A)(+) RNA in the cytoplasm following actinomycin D treatment. We discuss a role of JKTBP in mRNA nuclear export.

3T3 Cells↗