Regulation of a Myb transcription factor by cyclin-dependent kinase 2 in Giardia lamblia
Journal
Journal of Biological Chemistry
Journal Volume
287
Journal Issue
6
Pages
3733-3750
Date Issued
2012
Author(s)
Abstract
The protozoan Giardia lamblia parasitizes the human small intestine to cause diseases. It undergoes differentiation into infectious cysts by responding to intestinal stimulation.Howthe activated signal transduction pathways relate to encystation stimulation remain largely unknown. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately up-regulated by aMyb2transcription 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.Wehave 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, overexpression 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. ? 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
SDGs
Other Subjects
Activated signal; Catalytic residue; CDK inhibitors; Cell cycle regulation; Cell cycle regulators; Cell differentiation; Cyclin-dependent kinase; Genes encoding; Genome database; Giardia; Giardia lamblia; Kinase activity; MYB transcription factors; Over-expression; Small intestine; Up-regulation; Cytology; Genes; Phosphorylation; Protozoa; Signal transduction; Transcription factors; Enzymes; cyclin dependent kinase 2; protein Myb; article; cdk2 gene; controlled study; cwp gene; cyst formation; cytoplasm; enzyme activity; gene; gene expression; Giardia lamblia; mutation; nonhuman; parasite phenomena and functions; priority journal; protein localization; protein phosphorylation; upregulation; Cyclin-Dependent Kinase 2; Cytoplasm; Giardia lamblia; Humans; Oncogene Proteins v-myb; Phosphorylation; Protozoan Proteins; Transcription Factors; Giardia; Giardia intestinalis; Protozoa
Type
journal article