Am working on a essential gene for bacterial growth. In silico virtual studies based small molecule has been identified and studied in vitro.
We expected, when a protein is inhibited for its function, the gene expression of that particular protein may over express to make it survival. ?
Its my hypothesis valid or scientifically approachable ?
Drug targeting a genes end product protein, will it affect the gene to overexpress or downregulated ?
The phenomenon of treatment-induced overexpression of a target protein is indeed a possible mechanism of compensatory drug resistance that is well recognized in bacterial and mammalian systems.
Your hypothesis is valid and can be confirmed by a clear cause-and-effect overexpression of the target protein and the development of resistance (by increased survival related to such overexpression) that are related to exposure to the small molecule drug. The primary endpoint relationships to elucidate include temporal association of the development of resistance/overexpression in response to drug exposure and the quantification/magnitude of such overexpression of the target protein in response to drug exposure. The target protein specific functional activity may also in some cases be increased as well. The proof of increased mRNA expression associated with target protein is very convincing when combined with the foregoing.
In many cases there is upregulation of target protein expression as a consequence of drug exposure. There may be down regulation in the event there is direct genomic and/or translational targeting affecting expression.
It sounds like you have a very good and interesting observation that is important to characterize.
Thanks
Best
Fred
Thanks a lot for your valuable time spent for me. Can You share some references if possible.
Thanks again sir.
Jiao T. Wang, Wei Liu a , Hailin Tang a,c , Hongwei Xie. Screening drug target proteins based on sequence information. Journal of Biomedical Informatics 49 (2014) 269–274.
Chadalapaka G, Jutooru I, Burghardt R, Safe S. DRUGS THAT TARGET SPECIFICITY PROTEINS DOWNREGULATE EPIDERMAL GROWTH FACTOR RECEPTOR IN BLADDER CANCER CELLS. Molecular cancer research : MCR. 2010;8(5):739-750. doi:10.1158/1541-7786.MCR-09-0493.
Dear Dr. Entedhar Sarhat,
Thank you very much for your generous mind and for sharing the apt references. I gone through the same. Thanks a lot once again.
Regards
Murugan N
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