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

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

doi:10.5455/ajvs.285213

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Original Article

AJVS. 2018; 56(1): 81-87

doi: 10.5455/ajvs.285213

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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How to Cite this Article

Pubmed Style

Haggag YN, Nossair MA, Elaadli H, Mackey Z. 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

Haggag YN, Nossair MA, Elaadli H, Mackey Z. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. https://www.alexjvs.com/?mno=285213 [Access: May 05, 2025]. doi:10.5455/ajvs.285213

AMA (American Medical Association) Style

Haggag YN, Nossair MA, Elaadli H, Mackey Z. 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

Haggag YN, Nossair MA, Elaadli H, Mackey Z. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. AJVS. (2018), [cited May 05, 2025]; 56(1): 81-87. doi:10.5455/ajvs.285213

Harvard Style

Haggag, Y. N., Nossair, . M. A., Elaadli, . H. & Mackey, . Z. (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

Haggag, Yasser N., Mohammad A. Nossair, Haitham Elaadli, and 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

Haggag, Yasser N., Mohammad A. Nossair, Haitham Elaadli, and 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

APA (American Psychological Association) Style

Haggag, Y. N., Nossair, . M. A., Elaadli, . H. & Mackey, . Z. (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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