Mammalian target of rapamycin (mTORc1), Jagged 1, Jagged 2, Notch 1, Notch receptor
intracellular domain (NICD), and p27kip1 antibodies were from Santa Cruz Biotechnology (USA).
Direct contact of receptor and ligand triggers a series of proteolytic events at the level of the NOTCH receptor
, causing the receptor's intracellular domain to translocate to the nucleus where it activates transcription of target genes Hes and Hey (figure 1).
The researchers chose to investigate one of the proteins that acts in this pathway by binding to the Notch receptor
Jagged and Delta interact with the Notch receptor
on the cell surface to initiate the conformational change in the Notch extracellular domain .
Moreover, Wang says, the role his team has described for the Notch receptor
in angiogenesis makes the molecule a potential target of drugs for head-and-neck cancers and perhaps for other solid tumors.
have been found deregulated in many tumors, and the prevalence and location of mutations within each Notch receptor
coding gene varied considerably according to the tumor type .
They also observed upregulation of the Notch pathway in breast cancer stem cells via upregulation of Notch receptor
The extracellular domain (NECD) of the Notch receptor
is pulled away from the intracellular domain (NICD) exposing a site at which two proteolytic cleavage events occur.
However, recent animal studies have demonstrated that pharmacological inhibition of cell signalling via Notch receptors
using gamma-secretase inhibitors (GSIs) can regenerate hair cells and partially restore hearing capacity.
Four Notch receptors
(Notch1-4) and five Notch ligands (Delta-like1, 3, 4, and Jagged1, 2) have been identified in mammals.
are evolutionarily conserved cell surface receptors important for cell fate decisions and embryonic development (Osborne and Minter 2007).