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Regulation of a Myb Transcription Factor by Cyclin-dependent Kinase 2 in Giardia lamblia.

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Title: Regulation of a Myb Transcription Factor by Cyclin-dependent Kinase 2 in Giardia lamblia.
Authors: Chao-Cheng Cho1, Li-Hsin Su1, Yu-Chang Huang1, Yu-Jiao Pan1, Chin-Hung Sun1 chinhsun@ntu.edu.tw
Source: Journal of Biological Chemistry. 2/3/2012, Vol. 287 Issue 6, p3733-3750. 21p.
Subjects: Giardia lamblia, Transcription factors, Phosphorylation, Gene expression, Proteins
Abstract: The protozoan Giardia lamblia parasitizes the human small intestine to cause diseases. It undergoes differentiation into infectious cysts by responding to intestinal stimulation. How the activated signal transduction pathways relate to encystation stimulation remain largely unknown. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately up-regulated by a Myb2 transcription factor. Because cell differentiation is linked to cell cycle regulation, we tried to understand the role of cell cycle regulators, cyclin-dependent kinases (Cdks), in encystation. We found that the recombinant Myb2 was phosphorylated by Cdk-associated complexes and the levels of phosphorylation increased significantly during encystation. We have identified a putative cdk gene (cdk2) by searching the Giardia genome database. Cdk2 was found to localize in the cytoplasm with higher expression during encystation. Interestingly, over-expression of Cdk2 resulted in a significant increase of the levels of cwp gene expression and cyst formation. In addition, the Cdk2-associated complexes can phosphorylate Myb2 and the levels of phosphorylation increased significantly during encystation. Mutations of important catalytic residues of Cdk2 resulted in a significant decrease of kinase activity and ability of inducing cyst formation. Addition of a Cdk inhibitor, purvalanol A, significantly decreased the Cdk2 kinase activity and the levels of cwp gene expression and cyst formation. Our results suggest that the Cdk2 pathway may be involved in phosphorylation of Myb2, leading to activation of the Myb2 function and up-regulation of cwp genes during encystation. The results provide insights into the use of Cdk inhibitory drugs in disruption of Giardia differentiation into cysts. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Regulation of a Myb Transcription Factor by Cyclin-dependent Kinase 2 in Giardia lamblia.
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  Data: <searchLink fieldCode="AR" term="%22Chao-Cheng+Cho%22">Chao-Cheng Cho</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Li-Hsin+Su%22">Li-Hsin Su</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Yu-Chang+Huang%22">Yu-Chang Huang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Yu-Jiao+Pan%22">Yu-Jiao Pan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chin-Hung+Sun%22">Chin-Hung Sun</searchLink><relatesTo>1</relatesTo><i> chinhsun@ntu.edu.tw</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 2/3/2012, Vol. 287 Issue 6, p3733-3750. 21p.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22Giardia+lamblia%22">Giardia lamblia</searchLink><br /><searchLink fieldCode="DE" term="%22Transcription+factors%22">Transcription factors</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphorylation%22">Phosphorylation</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Proteins%22">Proteins</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The protozoan Giardia lamblia parasitizes the human small intestine to cause diseases. It undergoes differentiation into infectious cysts by responding to intestinal stimulation. How the activated signal transduction pathways relate to encystation stimulation remain largely unknown. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately up-regulated by a Myb2 transcription factor. Because cell differentiation is linked to cell cycle regulation, we tried to understand the role of cell cycle regulators, cyclin-dependent kinases (Cdks), in encystation. We found that the recombinant Myb2 was phosphorylated by Cdk-associated complexes and the levels of phosphorylation increased significantly during encystation. We have identified a putative cdk gene (cdk2) by searching the Giardia genome database. Cdk2 was found to localize in the cytoplasm with higher expression during encystation. Interestingly, over-expression of Cdk2 resulted in a significant increase of the levels of cwp gene expression and cyst formation. In addition, the Cdk2-associated complexes can phosphorylate Myb2 and the levels of phosphorylation increased significantly during encystation. Mutations of important catalytic residues of Cdk2 resulted in a significant decrease of kinase activity and ability of inducing cyst formation. Addition of a Cdk inhibitor, purvalanol A, significantly decreased the Cdk2 kinase activity and the levels of cwp gene expression and cyst formation. Our results suggest that the Cdk2 pathway may be involved in phosphorylation of Myb2, leading to activation of the Myb2 function and up-regulation of cwp genes during encystation. The results provide insights into the use of Cdk inhibitory drugs in disruption of Giardia differentiation into cysts. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1074/jbc.M111.298893
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        Text: English
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        PageCount: 21
        StartPage: 3733
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        Type: general
      – SubjectFull: Transcription factors
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      – SubjectFull: Phosphorylation
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      – SubjectFull: Gene expression
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      – SubjectFull: Proteins
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      – TitleFull: Regulation of a Myb Transcription Factor by Cyclin-dependent Kinase 2 in Giardia lamblia.
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            NameFull: Chao-Cheng Cho
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            NameFull: Li-Hsin Su
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            NameFull: Yu-Chang Huang
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            NameFull: Yu-Jiao Pan
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            NameFull: Chin-Hung Sun
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              Text: 2/3/2012
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              Y: 2012
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