Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celle...

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Published in:PloS one 2013-06, Vol.8 (6), p.e67327-e67327
Main Authors: Monnerat, Séverine, Almeida Costa, Cristina I, Forkert, Andrea C, Benz, Corinna, Hamilton, Alana, Tetley, Laurence, Burchmore, Richard, Novo, Carlos, Mottram, Jeremy C, Hammarton, Tansy C
Format: Article
Language:English
Subjects:
Animals
Biology
Cdc2 protein
Cell cycle
Cell Proliferation - genetics
Cyclin-dependent kinase
Cyclin-dependent kinases
Cyclins
Cyclins - genetics
Cyclins - metabolism
Cytokinesis
Endocytosis
Eukaryotes
Gene expression
Infections
Inflammation
Kinases
Life cycle engineering
Life cycles
Medicine
Mice
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Parasitology
Protein kinase
Protein kinase C
Protein kinases
Proteins
Proto-Oncogene Proteins c-crk - genetics
Proto-Oncogene Proteins c-crk - metabolism
Protozoa
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Ribonucleic acid
RNA
RNA polymerase
RNA-mediated interference
Transcription
Trypanosoma brucei
Trypanosoma brucei brucei - genetics
Trypanosoma brucei brucei - metabolism
Trypanosomiasis
Trypanosomiasis, African - genetics
Trypanosomiasis, African - metabolism
Vector-borne diseases
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cited_by cdi_FETCH-LOGICAL-c593t-719f52881e530fc48604e415f547ea32ec3ac2978ac7ccbf4f5a23033c3c15f23
cites cdi_FETCH-LOGICAL-c593t-719f52881e530fc48604e415f547ea32ec3ac2978ac7ccbf4f5a23033c3c15f23
container_end_page e67327
container_issue 6
container_start_page e67327
container_title PloS one
container_volume 8
creator Monnerat, Séverine
Almeida Costa, Cristina I
Forkert, Andrea C
Benz, Corinna
Hamilton, Alana
Tetley, Laurence
Burchmore, Richard
Novo, Carlos
Mottram, Jeremy C
Hammarton, Tansy C
description The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively.
doi_str_mv 10.1371/journal.pone.0067327
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Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23805309</pmid><doi>10.1371/journal.pone.0067327</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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issn 1932-6203
1932-6203
language eng
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source Publicly Available Content Database; PubMed Central
subjects Animals
Biology
Cdc2 protein
Cell cycle
Cell Proliferation - genetics
Cyclin-dependent kinase
Cyclin-dependent kinases
Cyclins
Cyclins - genetics
Cyclins - metabolism
Cytokinesis
Endocytosis
Eukaryotes
Gene expression
Infections
Inflammation
Kinases
Life cycle engineering
Life cycles
Medicine
Mice
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Parasitology
Protein kinase
Protein kinase C
Protein kinases
Proteins
Proto-Oncogene Proteins c-crk - genetics
Proto-Oncogene Proteins c-crk - metabolism
Protozoa
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Ribonucleic acid
RNA
RNA polymerase
RNA-mediated interference
Transcription
Trypanosoma brucei
Trypanosoma brucei brucei - genetics
Trypanosoma brucei brucei - metabolism
Trypanosomiasis
Trypanosomiasis, African - genetics
Trypanosomiasis, African - metabolism
Vector-borne diseases
title Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei
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