NF-κB-mediated repression of growth arrest- and DNA-damage-inducible proteins 45α and γ is essential for cancer cell survival Academic Article uri icon

Overview

MeSH Major

  • DNA Damage
  • Gene Expression Regulation, Neoplastic
  • NF-kappa B
  • Neoplasms
  • Proteins

abstract

  • The NF-kappaB/IkappaB signaling pathway is a critical regulator of cell survival in cancer. Here, we report that combined down-regulation of growth arrest- and DNA-damage-inducible proteins (GADD)45alpha and gamma expression by NF-kappaB is an essential step for various cancer types to escape programmed cell death. We demonstrate that inhibition of NF-kappaB in cancer cells results in GADD45alpha- and gamma-dependent induction of apoptosis and inhibition of tumor growth. Inhibition of GADD45alpha and gamma in cancer cells by small interfering RNA abrogates apoptosis induction by the inhibitor of NF-kappaB and blocks c-Jun N-terminal kinase activation, whereas overexpression of GADD45alpha and gamma activates c-Jun N-terminal kinase and induces apoptosis. These results establish an unambiguous role for the GADD45 family as an essential mediator of cell survival in cancer cells with implications for cancer chemotherapy and novel drug discovery.

publication date

  • September 14, 2004

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC518803

Digital Object Identifier (DOI)

  • 10.1073/pnas.0402069101

PubMed ID

  • 15353598

Additional Document Info

start page

  • 13618

end page

  • 23

volume

  • 101

number

  • 37