Tab3 Out of the Array

Science's STKE  12 Nov 2002:
Vol. 2002, Issue 158, pp. tw422
DOI: 10.1126/stke.2002.158.tw422

Inhibition of bone morphogenic protein (BMP) signaling leads to neuralization early in embryonic development. Known inhibitors are either secreted proteins that interfere with ligand-receptor interactions or intracellular proteins that block signaling emanating from the receptor. Muñoz-Sanjuán et al. used an array of transcripts from normal Xenopus gastrula-stage embryos and from Smad7-injected embryos (which are neuralized) to identify patterns of gene expression associated with neural induction. One unexpected trend from the analysis was that more genes encoding proteins that function in posttranscriptional and translational regulation were identified than genes involved in transcriptional regulation. Selected clones were subjected to additional analysis, including an assay for neuralizing ability when injected into Xenopus explants. One such clone was Tab3, for TGF-β-activated kinase (Tak1)-binding protein. Tab3 was expressed in neural tissues in the developing embryo and tadpole. Injection of Tab3 RNA into Xenopus explants stimulated the expression of neural markers and injection of a putative dominant-negative version of Tab3 stimulated epidermal marker expression, consistent with stimulation of BMP signaling. Tab proteins serve as a site of cross talk among downstream signaling cascades [p38, j-NH2-terminal kinase (JNK), and NF-κB]. Tab2 and Tab3 have conserved ubiquitin ligase-binding domains. Thus, implication of Tab3 in neural fate specification expands the potential pathways involved in this process.

I. Muñoz-Sanjuán, E. Bell, C. R. Altmann, A. Vonica, A. H. Brivanlou, Gene profiling during neural induction in Xenopus laevis: Regulation of BMP signaling by post-transcriptional mechanisms and TAB3, a novel TAK1-binding protein. Development 129, 5529-5540 (2002). [Abstract] [Full Text]