PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells.
The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology.
Noguchi
Hirofumi
H
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Kaneto
Hideaki
H
Weir
Gordon C
GC
Bonner-Weir
Susan
S
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D010183:Pancreatic Ducts / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein