Rather than sitting in awe before this dangerous phenomena that is the NOTCH, It is time to take a closer look at a comprehensive corrective measures to face it. Mutations at the NOTCH involve many killer cancers. Our patients are dying when we "navigate" cautiously with timid treatments!
We know the NOTCH has a Membrane base but "lightning fast" involves epigenetic and nuclear events. It is time to take a stand and face this monstrous challenge in a more systematic way. Again c-MYC is a critical Mediator of the Notch activity, it is therefore a potential good Biomarker of its activity. This NOTCH first described in Hematologic disease (it is involved with t(7,9) translocation) gives a powerful message of "apoptosis consensus to leukemic cell" most likely by its relations with the AKT/MTOR implications.
It is a Membrane based and act
1.as a Receptors and theirs various Co-factors (affected by CYTOKINES (IL21,granzyme), GROWTH FACTORS (TGF beta), and NEUROFACTORS), Endophilin,MAML1,
2.As a Endocytototic apparatus, indeed the internal portion of these proteins enter the cell after Detachment (FAK involved)
3.It is affected by important molecules at the membranes (Cyclic AMP, secretases, an the Hedghog pathway, ions channels, Rho-GTPase)
It goes on in the Cytosol where transporters must be involved
and affects main pathways through some anchors and related co-activators/adaptators (Grb2) and interact with wild genes FYN, SMRTR, Six1,dHBP1,TRAF6, HSP60-90,Ctip-2
some of its related proteins will undergo Ubiquilation E6
It goes on to the Nucleus to affect epigenetic events miR524, c-MYC, SMAD7, HES promoter,
Here is summarized work of many researchers, we thank them for their ccontibutions, but it is time to stop admiring Mutations at NOTCH, and take a stand!
No comments:
Post a Comment