E-ISSN 2536-9520 | ISSN 1110-2047
 

Original Research (Original Article) 


Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey.

Abstract
Proliferating cell nuclear antigen (PCNA) coordinates many functions including cell cycle progression and DNA replication in eukaryotic cells. Inhibition of the PCNA protein function in Trypanosoma brucei could be a new strategy in controlling Human African Trypanosomiasis. In the present study, we explored the function of TbPCNA by deregulation the protein expression through the overexpression, and by applying the small molecule inhibition. Overexpression of human PCNA or T. brucei PCNA wild-type proteins inhibits the parasite proliferation. On the other hand, T. brucei that overexpress the HsPCNA M40A or TbPCNA M40A mutants grew normally, indicating that inhibition of PIP-box protein interaction is important for the lethal phenotype. In testing this hypothesis, we applied the small molecule inhibitor T2 amino alcohol (T2AA). Proliferation in parasites that overexpress HsPCNA resumed after T2AA treatment, but not parasites that overexpressed TbPCNA. We concluded that T2AA selectively inhibits HsPCNA not TbPCNA. This data presented here will be a prerequisite for investigating TbPCNA interacting proteins and discovering inhibitors that specifically target TbPCNA to kill the parasite.

Key words: T2 amino alcohol, proliferating cell nuclear antigen and Trypanosoma brucei.


 
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Pubmed Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. AJVS. 2018; 56(1): 81-87. doi:10.5455/ajvs.285213


Web Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. http://www.alexjvs.com/?mno=285213 [Access: December 12, 2018]. doi:10.5455/ajvs.285213


AMA (American Medical Association) Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. AJVS. 2018; 56(1): 81-87. doi:10.5455/ajvs.285213



Vancouver/ICMJE Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. AJVS. (2018), [cited December 12, 2018]; 56(1): 81-87. doi:10.5455/ajvs.285213



Harvard Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey (2018) Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. AJVS, 56 (1), 81-87. doi:10.5455/ajvs.285213



Turabian Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. 2018. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. Alexandria Journal of Veterinary Sciences, 56 (1), 81-87. doi:10.5455/ajvs.285213



Chicago Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. "Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei." Alexandria Journal of Veterinary Sciences 56 (2018), 81-87. doi:10.5455/ajvs.285213



MLA (The Modern Language Association) Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey. "Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei." Alexandria Journal of Veterinary Sciences 56.1 (2018), 81-87. Print. doi:10.5455/ajvs.285213



APA (American Psychological Association) Style

Yasser N. Haggag, Mohammad A. Nossair, Haitham Elaadli, Zachary Mackey (2018) Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. Alexandria Journal of Veterinary Sciences, 56 (1), 81-87. doi:10.5455/ajvs.285213





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