Literature DB >> 27018127

A novel protein kinase is essential in bloodstream Trypanosoma brucei.

Bryan C Jensen1, Nick Booster1, Rama Subba Rao Vidadala2, Dustin J Maly3, Marilyn Parsons4.   

Abstract

Human African trypanosomiasis a fatal disease for which no vaccines exist and treatment regimens are difficult. Here, we evaluate a Trypanosoma brucei protein kinase, AEK1, as a potential drug target. Conditional knockouts confirmed AEK1 essentiality in bloodstream forms. For chemical validation, we overcame the lack of AEK1 inhibitors by creating parasites expressing a single, functional analog-sensitive AEK1 allele. Analog treatment of mice infected with this strain delayed parasitemia and death, with one-third of animals showing no parasitemia. These studies validate AEK1 as a drug target and highlight the need for further understanding of its function.
Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  AGC kinase; Analog-sensitive; Drug target; In vivo; Protein kinase; Trypanosome

Mesh:

Substances:

Year:  2016        PMID: 27018127      PMCID: PMC4925258          DOI: 10.1016/j.ijpara.2016.03.001

Source DB:  PubMed          Journal:  Int J Parasitol        ISSN: 0020-7519            Impact factor:   3.981


  28 in total

1.  Future treatment options for human African trypanosomiasis.

Authors:  Amy J Jones; Vicky M Avery
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2.  A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei.

Authors:  E Wirtz; S Leal; C Ochatt; G A Cross
Journal:  Mol Biochem Parasitol       Date:  1999-03-15       Impact factor: 1.759

Review 3.  A historical overview of protein kinases and their targeted small molecule inhibitors.

Authors:  Robert Roskoski
Journal:  Pharmacol Res       Date:  2015-07-21       Impact factor: 7.658

4.  Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity.

Authors:  Steven M Johnson; Ryan C Murphy; Jennifer A Geiger; Amy E DeRocher; Zhongsheng Zhang; Kayode K Ojo; Eric T Larson; B Gayani K Perera; Edward J Dale; Panqing He; Molly C Reid; Anna M W Fox; Natascha R Mueller; Ethan A Merritt; Erkang Fan; Marilyn Parsons; Wesley C Van Voorhis; Dustin J Maly
Journal:  J Med Chem       Date:  2012-02-27       Impact factor: 7.446

5.  Identification of essential and non-essential protein kinases by a fusion PCR method for efficient production of transgenic Trypanosoma brucei.

Authors:  Christopher Merritt; Kenneth Stuart
Journal:  Mol Biochem Parasitol       Date:  2013-05-16       Impact factor: 1.759

6.  Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen.

Authors:  Nathaniel G Jones; Elizabeth B Thomas; Elaine Brown; Nicholas J Dickens; Tansy C Hammarton; Jeremy C Mottram
Journal:  PLoS Pathog       Date:  2014-01-16       Impact factor: 6.823

7.  Extensive stage-regulation of translation revealed by ribosome profiling of Trypanosoma brucei.

Authors:  Bryan C Jensen; Gowthaman Ramasamy; Elton J R Vasconcelos; Nicholas T Ingolia; Peter J Myler; Marilyn Parsons
Journal:  BMC Genomics       Date:  2014-10-20       Impact factor: 3.969

8.  An analogue-sensitive approach identifies basal body rotation and flagellum attachment zone elongation as key functions of PLK in Trypanosoma brucei.

Authors:  Ana Lozano-Núñez; Kyojiro N Ikeda; Thomas Sauer; Christopher L de Graffenried
Journal:  Mol Biol Cell       Date:  2013-02-27       Impact factor: 4.138

9.  Comparative SILAC proteomic analysis of Trypanosoma brucei bloodstream and procyclic lifecycle stages.

Authors:  Michael D Urbaniak; M Lucia S Guther; Michael A J Ferguson
Journal:  PLoS One       Date:  2012-05-04       Impact factor: 3.240

Review 10.  Treatment options for second-stage gambiense human African trypanosomiasis.

Authors:  Gilles Eperon; Manica Balasegaram; Julien Potet; Charles Mowbray; Olaf Valverde; François Chappuis
Journal:  Expert Rev Anti Infect Ther       Date:  2014-09-10       Impact factor: 5.091

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  3 in total

1.  Rapid block of pre-mRNA splicing by chemical inhibition of analog-sensitive CRK9 in Trypanosoma brucei.

Authors:  Ujwala Gosavi; Ankita Srivastava; Nitika Badjatia; Arthur Günzl
Journal:  Mol Microbiol       Date:  2020-03-04       Impact factor: 3.501

2.  SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes.

Authors:  Andreu Saura; Paula A Iribarren; Domingo Rojas-Barros; Jean M Bart; Diana López-Farfán; Eduardo Andrés-León; Isabel Vidal-Cobo; Cordula Boehm; Vanina E Alvarez; Mark C Field; Miguel Navarro
Journal:  EMBO Rep       Date:  2019-11-06       Impact factor: 9.071

3.  Drug Target Validation of the Protein Kinase AEK1, Essential for Proliferation, Host Cell Invasion, and Intracellular Replication of the Human Pathogen Trypanosoma cruzi.

Authors:  Miguel A Chiurillo; Bryan C Jensen; Roberto Docampo
Journal:  Microbiol Spectr       Date:  2021-09-29
  3 in total

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