Showing posts with label modulators. Show all posts
Showing posts with label modulators. Show all posts

Thursday, January 17, 2013

POLYUBIQUITINATION

The rise of the role of antiproteasome in the treatment of hematologic malignancies such Multiple Myeloma
requires us to stop a bit and reflect on the basic role of proteasomes which is to destroy used proteins.  To be recognized as old proteins ready for destruction, the protein is Ubiquitinated and ready for disposal.  The anti-proteasomes in effect block this plan.  And sure enough, Ubiquitinated proteins stay alive longer and guess what, it is an ubiquitinated proteins that seems to contribute to the negative effect on Modulators of pathways.   Ubiquitinated proteins forms stops transcriptions factors at check points, block the NF-kB, and drives the effects of Antiproteasomes.
Can a simple infusion of ubiquitinated TNF blocks its effects, can we start just ubiquitinating growth factors and infuse them to stop infectious process or cancer growth?  Remember, DRIVER Pathways are driven most of the time by regulators who seems to have a negative feedback from UBIQUITINATED specific pathway proteins in general terms (rare exception will exist)! What do you think?  Can a polyubiquitinated growth factor still stimulate effectively its receptor or will it dampen the stimulation and slow the devastating effect of say, TNF?