Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus.
Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases essential for cell cycle progression. Herein, we describe the participation of CDKs in the physiology of Rhipicephalus microplus, the southern cattle tick and an important disease vector. Firstly, amino acid sequences homologou...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3795742?pdf=render |
_version_ | 1828880718228357120 |
---|---|
author | Helga Gomes Nelilma C Romeiro Gloria R C Braz Eduardo Alves Gamosa de Oliveira Camilla Rodrigues Rodrigo Nunes da Fonseca Naftaly Githaka Masayoshi Isezaki Satoru Konnai Kazuhiko Ohashi Itabajara da Silva Vaz Carlos Logullo Jorge Moraes |
author_facet | Helga Gomes Nelilma C Romeiro Gloria R C Braz Eduardo Alves Gamosa de Oliveira Camilla Rodrigues Rodrigo Nunes da Fonseca Naftaly Githaka Masayoshi Isezaki Satoru Konnai Kazuhiko Ohashi Itabajara da Silva Vaz Carlos Logullo Jorge Moraes |
author_sort | Helga Gomes |
collection | DOAJ |
description | Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases essential for cell cycle progression. Herein, we describe the participation of CDKs in the physiology of Rhipicephalus microplus, the southern cattle tick and an important disease vector. Firstly, amino acid sequences homologous with CDKs of other organisms were identified from a R. microplus transcriptome database in silico. The analysis of the deduced amino acid sequences of CDK1 and CDK10 from R. microplus showed that both have caspase-3/7 cleavage motifs despite their differences in motif position and length of encoded proteins. CDK1 has two motifs (DKRGD and SAKDA) located opposite to the ATP binding site while CDK10 has only one motif (SLLDN) for caspase 3-7 near the ATP binding site. Roscovitine (Rosco), a purine derivative that inhibits CDK/cyclin complexes by binding to the catalytic domain of the CDK molecule at the ATP binding site, which prevents the transfer of ATP's γphosphoryl group to the substrate. To determine the effect of Rosco on tick CDKs, BME26 cells derived from R. microplus embryo cells were utilized in vitro inhibition assays. Cell viability decreased in the Rosco-treated groups after 24 hours of incubation in a concentration-dependent manner and this was observed up to 48 hours following incubation. To our knowledge, this is the first report on characterization of a cell cycle protein in arachnids, and the sensitivity of BME26 tick cell line to Rosco treatment suggests that CDKs are potential targets for novel drug design to control tick infestation. |
first_indexed | 2024-12-13T09:53:11Z |
format | Article |
id | doaj.art-6aaa89a2e59641b1a3f8d37b0d2b8133 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-13T09:53:11Z |
publishDate | 2013-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-6aaa89a2e59641b1a3f8d37b0d2b81332022-12-21T23:51:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7612810.1371/journal.pone.0076128Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus.Helga GomesNelilma C RomeiroGloria R C BrazEduardo Alves Gamosa de OliveiraCamilla RodriguesRodrigo Nunes da FonsecaNaftaly GithakaMasayoshi IsezakiSatoru KonnaiKazuhiko OhashiItabajara da Silva VazCarlos LogulloJorge MoraesCyclin-dependent kinases (CDKs) are a family of serine/threonine kinases essential for cell cycle progression. Herein, we describe the participation of CDKs in the physiology of Rhipicephalus microplus, the southern cattle tick and an important disease vector. Firstly, amino acid sequences homologous with CDKs of other organisms were identified from a R. microplus transcriptome database in silico. The analysis of the deduced amino acid sequences of CDK1 and CDK10 from R. microplus showed that both have caspase-3/7 cleavage motifs despite their differences in motif position and length of encoded proteins. CDK1 has two motifs (DKRGD and SAKDA) located opposite to the ATP binding site while CDK10 has only one motif (SLLDN) for caspase 3-7 near the ATP binding site. Roscovitine (Rosco), a purine derivative that inhibits CDK/cyclin complexes by binding to the catalytic domain of the CDK molecule at the ATP binding site, which prevents the transfer of ATP's γphosphoryl group to the substrate. To determine the effect of Rosco on tick CDKs, BME26 cells derived from R. microplus embryo cells were utilized in vitro inhibition assays. Cell viability decreased in the Rosco-treated groups after 24 hours of incubation in a concentration-dependent manner and this was observed up to 48 hours following incubation. To our knowledge, this is the first report on characterization of a cell cycle protein in arachnids, and the sensitivity of BME26 tick cell line to Rosco treatment suggests that CDKs are potential targets for novel drug design to control tick infestation.http://europepmc.org/articles/PMC3795742?pdf=render |
spellingShingle | Helga Gomes Nelilma C Romeiro Gloria R C Braz Eduardo Alves Gamosa de Oliveira Camilla Rodrigues Rodrigo Nunes da Fonseca Naftaly Githaka Masayoshi Isezaki Satoru Konnai Kazuhiko Ohashi Itabajara da Silva Vaz Carlos Logullo Jorge Moraes Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus. PLoS ONE |
title | Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus. |
title_full | Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus. |
title_fullStr | Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus. |
title_full_unstemmed | Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus. |
title_short | Identification and structural-functional analysis of cyclin-dependent kinases of the cattle tick Rhipicephalus (Boophilus) microplus. |
title_sort | identification and structural functional analysis of cyclin dependent kinases of the cattle tick rhipicephalus boophilus microplus |
url | http://europepmc.org/articles/PMC3795742?pdf=render |
work_keys_str_mv | AT helgagomes identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT nelilmacromeiro identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT gloriarcbraz identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT eduardoalvesgamosadeoliveira identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT camillarodrigues identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT rodrigonunesdafonseca identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT naftalygithaka identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT masayoshiisezaki identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT satorukonnai identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT kazuhikoohashi identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT itabajaradasilvavaz identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT carloslogullo identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus AT jorgemoraes identificationandstructuralfunctionalanalysisofcyclindependentkinasesofthecattletickrhipicephalusboophilusmicroplus |