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This version published online on August 23, 2007
Endocrinology, doi:10.1210/en.2007-0636
A more recent version of this article appeared on November 1, 2007
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Submitted on May 14, 2007
Accepted on August 10, 2007

Pax4 Paired Domain Mediates Direct Protein Transduction into Mammalian Cells

Jun Lu, Ge Li, Michael S. Lan, Shuyu Zhang, Weiwei Fan, Hongwei Wang, and Daru Lu*

State Key Laboratory of Genetic Engineering, School of Life Science, University of Fudan, Shanghai 200433, China; and Department of Pediatrics, LSUHSC, the Research Institute for Children, Children's Hospital, New Orleans, LA 70118

* To whom correspondence should be addressed. E-mail: drlu{at}fudan.edu.cn.

Pax4, a paired-box transcription factor, is a key regulator of pancreatic islet cell growth and differentiation. Here, we report for the first time that the Pax4 protein can permeate into various cell types including pancreatic islets. The paired domain of Pax4 served as a novel protein transduction domain (PTD). The Pax4 protein can transduce in a dose- and time-dependent manner. The cellular uptake of Pax4 PTD can be completely blocked by heparin, whereas cytochalasin D and amiloride were partially effective in blocking the Pax4 protein entry. Transduced intact Pax4 protein functions similarly to the endogenous Pax4. It inhibits the Pax6 mediated transactivation and protects Min6 cells against TNF{alpha} induced apoptosis. These data suggest that Pax4 protein transduction could be a safe and valuable strategy for protecting islet cell growth in culture from apoptosis and promoting islet cell differentiation.
Key words: Pax4 • Paired domain • Protein transduction domain




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