title: The cyclin-dependent kinase inhibitor KRP2 controls the onset of the endoreduplication cycle during Arabidopsis leaf development through inhibition of mitotic CDKA;1 kinase complexes.
abstract: Exit from the mitotic cell cycle and initiation of cell differentiation frequently coincides with the onset of endoreduplication, a modified cell cycle during which DNA continues to be duplicated in the absence of mitosis. Although the mitotic cell cycle and the endoreduplication cycle share much of the same machinery, the regulatory mechanisms controlling the transition between both cycles remain poorly understood. We show that the A-type cyclin-dependent kinase CDKA;1 and its specific inhibitor, the Kip-related protein, KRP2 regulate the mitosis-to-endocycle transition during Arabidopsis thaliana leaf development. Constitutive overexpression of KRP2 slightly above its endogenous level only inhibited the mitotic cell cycle-specific CDKA;1 kinase complexes, whereas the endoreduplication cycle-specific CDKA;1 complexes were unaffected, resulting in an increase in the DNA ploidy level. An identical effect on the endoreduplication cycle could be observed by overexpressing KRP2 exclusively in mitotically dividing cells. In agreement with a role for KRP2 as activator of the mitosis-to-endocycle transition, KRP2 protein levels were more abundant in endoreduplicating than in mitotically dividing tissues. We illustrate that KRP2 protein abundance is regulated posttranscriptionally through CDK phosphorylation and proteasomal degradation. KRP2 phosphorylation by the mitotic cell cycle-specific CDKB1;1 kinase suggests a mechanism in which CDKB1;1 controls the level of CDKA;1 activity through regulating KRP2 protein abundance. In accordance with this model, KRP2 protein levels increased in plants with reduced CDKB1;1 activity. Moreover, the proposed model allowed a dynamical simulation of the in vivo observations, validating the sufficiency of the regulatory interactions between CDKA;1, KRP2, and CDKB1;1 in fine-tuning the mitosis-to-endocycle transition.
authors.affiliation: Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Gent, Belgium.
authors.forename: Aurine
authors.initials: A
authors.lastname: Verkest
authors.forename: Carmem-Lara de O
authors.initials: CL
authors.lastname: Manes
authors.forename: Steven
authors.initials: S
authors.lastname: Vercruysse
authors.forename: Sara
authors.initials: S
authors.lastname: Maes
authors.forename: Els
authors.initials: E
authors.lastname: Van Der Schueren
authors.forename: Tom
authors.initials: T
authors.lastname: Beeckman
authors.forename: Pascal
authors.initials: P
authors.lastname: Genschik
authors.forename: Martin
authors.initials: M
authors.lastname: Kuiper
authors.forename: Dirk
authors.initials: D
authors.lastname: Inzé
authors.forename: Lieven
authors.initials: L
authors.lastname: De Veylder
mesh_terms: D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D018506:Gene Expression Regulation, Plant / Q000235:genetics; D046911:Macromolecular Substances / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D010766:Phosphorylation; D018515:Plant Leaves / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D011003:Ploidies; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D029681:Arabidopsis Proteins; D018797:Cell Cycle Proteins; C407546:ICK2 protein, Arabidopsis; D046911:Macromolecular Substances; C434472:CDKA1 protein, Arabidopsis; C435712:CDKB1;2 protein, Arabidopsis; D018844:Cyclin-Dependent Kinases; D046988:Proteasome Endopeptidase Complex