BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence

Hirofomi Noguchi, Susan Bonner-Weir, Fan Yan Wei, Masayuki Matsushita, Shinichi Matsumoto

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)

Abstract

BETA2/NeuroD, a basic helix-loop-helix transcription factor, is a key regulator of pancreatic islet morphogenesis and insulin gene transcription. Here we report for the first time that the BETA2/NeuroD protein can permeate several cells, including pancreatic islets, due to an arginine- and lysine-rich protein transduction domain sequence in its structure. The BETA2/NeuroD protein was transduced in a dose-dependent manner up to 1 μmol/l. Transduced BETA2/NeuroD functions similarly to endogenous BETA2/NeuroD: it binds to the insulin promoter and activates its expression. We also investigated the mechanism of BETA2/NeuroD protein transduction. The BETA2/NeuroD protein penetrated cells by macropinocytosis and was released from endosomes homogeneously in cytoplasm and nuclei. These data suggest that BETA2/NeuroD protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription without requiring gene transfer technology.

Original languageEnglish
Pages (from-to)2859-2866
Number of pages8
JournalDiabetes
Volume54
Issue number10
DOIs
Publication statusPublished - 2005 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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