PYRIN domain of NALP2 inhibits cell proliferation and tumor growth of human glioblastoma

Plasmid. 2010 Jul;64(1):41-50. doi: 10.1016/j.plasmid.2010.01.003. Epub 2010 Apr 11.

Abstract

NACHT leucine-rich domain and pyrin-containing protein 2 (NALP2) plays a crucial role in inflammation through regulation of NF-kappaB activity. The N-terminal PRYIN domain of NALP2 (PYD) functions similarly in inhibiting NF-kappaB activity. To investigate if NALP2 or PYD regulates cell proliferation or tumor growth of glioblastoma, lentiviruses carrying PYD (Lenti-PYD-Flag) was successfully packaged. Lenti-PYD-Flag is able to transduce tumor cells with high efficiency and mediate high expression of peptide PYD-Flag. Transduction with Lenti-PYD-Flag significantly inhibited cell proliferation and tumor growth of U-87 MG, but not other cell lines tested. PYD inhibited nuclear accumulation of endogenous p65. These findings imply that: (i) our pRRL-based lentiviral system can transduce tumor cells with high transduction efficiency, and mediate high level expression of, at least 1.8 kb, foreign genes; (ii) PYD inhibits cell proliferation and tumor growth of glioblastoma possibly through the inhibition of NF-kappaB activity, and PYD appears to be a promising candidate for the development of targeted therapy for glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Genetic Vectors / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Lentivirus / genetics
  • Mice
  • Neoplasm Invasiveness
  • Plasmids / genetics
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Transcription Factor RelA / metabolism
  • Transduction, Genetic
  • Tumor Necrosis Factor-alpha / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha