Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.108 (
TAT
)
2,389
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Stem cell technologies hold great potential for the treatment of type 1 diabetes, provided that functional transplantable beta-cells can be selectively generated in an efficient manner. Such a process should recapitulate, at least to a certain extent, the embryonic development of beta-cells in vitro. However, progress at identifying the transcription factors involved in beta-cell development has not been accompanied by a parallel success at unraveling the pattern of their instructive extracellular signals. Here we present proof of principle of a novel approach to circumvent this problem, based on the use of the HIV/TAT protein transduction domain.
Neurogenin 3
(
ngn3
), a factor whose expression is essential for pancreatic endocrine differentiation, was fused to the
TAT
domain. Administration of
TAT
/
ngn3
to cultured pancreatic explants results in efficient uptake, nuclear translocation, and stimulation of downstream reporter and endogenous genes. Consistent with the predicted activity of the protein, e9.5 and e13.5 mouse pancreatic explants cultured in the presence of
TAT
/
ngn3
show an increased level of endocrine differentiation compared with control samples. Our results raise the possibility of sequentially specifying stem/progenitor cells toward the beta-cell lineage, by using the appropriate sequence and combination of
TAT
-fused transcription factors.
...
PMID:TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro. 1573 48
