Growth inhibition of glioblastoma cells by human Purα

✍ Scribed by Nune Darbinian; Gary L. Gallia; James King; Luis Del Valle; Edward M. Johnson; Kamel Khalili

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 312 KB
• Volume: 189
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.10029

✦ Synopsis

Abstract

Purα is a multifunctional DNA‐ and RNA‐binding protein implicated in a variety of biological events including transcription and replication. Further, this protein has the ability to form a complex with several cellular proteins which are important for cell proliferation including the transcription factor, E2F‐1. Purα has a modular structure highlighted by alternating three basic aromatic class I and two acidic leucine‐rich class II repeats in the central region of the protein. Here, we demonstrate that ectopic overexpression of Purα suppresses proliferation of a variety of transformed and tumor cells including human glioblastoma. By utilizing various deletion mutants of Purα in colony formation assay, we identified the region spanning the first class II repeat (residues 107–131) and the second class I repeat (residues 148–170) of Purα which participate in growth inhibitory action of Purα. Results from protein transduction experiments using the synthetic peptides representing residues 109–131 and 123–154 of Purα in fusion with the arginine rich domain of HIV‐1 Tat revealed cellular internalization and nuclear appearance of the Tat–Purα fusion peptide after 2 h and its detection in nuclei up to 24 h after treatment. Glioblastoma cells treated with Tat–Purα (109–131) and Tat–Purα (123–154) exhibited 41 and 47% decrease, respectively, in proliferation. Altogether these results illustrate the efficacy of Purα in suppressing glioblastoma cell growth and provide evidence for the potential use of this protein and its derivative(s) in blocking proliferation of tumor cells. © 2001 Wiley‐Liss, Inc.