Preview
Sign-in for full Details 
Sign-in free and Explore the Exciting World of BiomedExperts:
- Over 1.500.000 Profiles
- More than 1.800 Organizations worldwide
- State of the Art Network Visualizations
- Manage your own Profile
- Locate Experts in your Country/Region
- Locate Experts in your 1. and 2. Level Network
- Connect to Experts Worldwide
find experts for
Sign-in to see more
2007:
Sarkar Devanand; Park Eun Sook; Barber Glen N; Fisher Paul B
Activation of double-stranded RNA dependent protein kinase, a new pathway by which human polynucleotide phosphorylase (hPNPase(old-35)) induces apoptosis.
Cancer research 2007;
67(
17):.
Human polynucleotide phosphorylase (hPNPase(old-35)) is a type I IFN-inducible 3',5' exoribonuclease that mediates mRNA degradation. In melanoma cells, slow and sustained overexpression of hPNPase(old-35) induces G(1) cell cycle arrest ultimately culminating in apoptosis, whereas rapid overexpression of hPNPase(old-35) directly promotes apoptosis without cell cycle changes. These observations imply that inhibition of cell cycle progression and induction of apoptosis by hPNPase(old-35) involve multiple intracellular targets and signaling pathways. We now provide evidence that the apoptosis-inducing activity of hPNPase(old-35) is mediated by activation of double-stranded RNA-dependent protein kinase (PKR). Activation of PKR by hPNPase(old-35) precedes phosphorylation of eukaryotic initiation factor-2alpha and induction of growth arrest and DNA damage-inducible gene 153 (GADD153) that culminates in the shutdown of protein synthesis and apoptosis. Activation of PKR by hPNPase(old-35) also instigates down-regulation of the antiapoptotic protein Bcl-x(L). A dominant-negative inhibitor of PKR, as well as GADD153 antisense or bcl-x(L) overexpression, effectively inhibits apoptosis induction by hPNPase(old-35). These studies elucidate a novel pathway by which an evolutionary conserved RNA-metabolizing enzyme, hPNPase(old-35), regulates cell growth and viability.
Post to CiteULike 
Sign in free and see...
Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more
