Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei
Joint Authors
al-Adili, Haytham
Hajjaj, Yasir N.
Mackey, Zachary
Nusayr, Muhammad A.
Source
Alexandria Journal of Veterinary Sciences
Issue
Vol. 56, Issue 1 (31 Jan. 2018), pp.81-87, 7 p.
Publisher
Alexandria University Faculty of Veterinary Medicine
Publication Date
2018-01-31
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Hajjaj, Yasir N.& Nusayr, Muhammad A.& al-Adili, Haytham& Mackey, Zachary. 2018. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. Alexandria Journal of Veterinary Sciences،Vol. 56, no. 1, pp.81-87.
https://search.emarefa.net/detail/BIM-1343015
Modern Language Association (MLA)
Hajjaj, Yasir N.…[et al.]. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. Alexandria Journal of Veterinary Sciences Vol. 56, no. 1 (Jan. 2018), pp.81-87.
https://search.emarefa.net/detail/BIM-1343015
American Medical Association (AMA)
Hajjaj, Yasir N.& Nusayr, Muhammad A.& al-Adili, Haytham& Mackey, Zachary. Selective inhibition of T2AA for human PCNA over PCNA homolog in Trypanosoma brucei. Alexandria Journal of Veterinary Sciences. 2018. Vol. 56, no. 1, pp.81-87.
https://search.emarefa.net/detail/BIM-1343015
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references : p. 85-87
Record ID
BIM-1343015