Accession Number:



Identification of NPM and DDX5 as Therapeutic Targets in TSC

Descriptive Note:

Technical Report,30 Sep 2015,29 Sep 2016

Corporate Author:

Washington University Saint Louis United States

Personal Author(s):

Report Date:


Pagination or Media Count:



TSC is a common inherited predisposition syndrome, affecting nearly 1 in 7,500 individuals. Individuals with TSC develop benign tumors in multiple organs, including the retina, skin, lung, kidney and brain. The identification of valid targets in TSC has been discouraging. In search of TSC targets, we recently identified NPM as a downstream effector of mTOR signaling in TSC cells, providing cells with an abundant supply of ribosomes necessary for supporting their increased growth rate. We now provide evidence that NPM forms a novel complex with DDX5 to drive TSC cell growth. Using the NCI diversity set of chemical compounds, we have now identified two compounds that potently inhibit split-luciferase activity in two TSC cells lines. Notably, these two compounds also inhibit the proliferation of TSCp53-null and UMB1949 TSC cells while not altering the growth rates of p53-null cells that maintain TSC function, suggesting that these compounds might specifically target NPM-DDX5 complex formation when it is enhanced in TSC cells. We will now move these exciting data forward with a larger library screen while also continuing to validate these two chemical compounds.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement: