Novel Functions of Plant Cyclin-Dependent Kinase Inhibitors, ICK1/KRP1, Can Act Non-Cell-Autonomously and Inhibit Entry into Mitosis

Abstract

In animals, cyclin-dependent kinase inhibitors (CKIs) are important regulators of cell cycle progression. Recently, putative CKIs were also identified in plants, and in previous studies, Arabidopsis thaliana plants misexpressing CKIs were found to have reduced endoreplication levels and decreased numbers of cells consistent with a function of CKIs in blocking the G1-S cell cycle transition. Here, we demonstrate that at least one inhibitor from Arabidopsis, ICK1/KRP1, can also block entry into mitosis but allows S-phase progression causing endoreplication. Our data suggest that plant CKIs act in a concentrationdependent manner and have an important function in cell proliferation as well as in cell cycle exit and in turning from a mitotic to an endoreplicating cell cycle mode. Endoreplication is usually associated with terminal differentiation; we observed, however, that cell fate specification proceeded independently from ICK1/KRP1-induced endoreplication. Strikingly, we found that endoreplicated cells were able to reenter mitosis, emphasizing the high degree of flexibility of plant cells during development. Moreover, we show that in contrast with animal CDK inhibitors, ICK1/KRP1 can move between cells. On the one hand, this challenges plant cell cycle control with keeping CKIs locally controlled, and on the other hand this provides a possibility of linking cell cycle control in single cells with the supracellular organization of a tissue or an organ.

T-Loop Phosphorylation ofArabidopsisCDKA;1 Is Required for Its Function and Can Be Partially Substituted by an Aspartate Residue

“…In contrast with the findings described above, weak misexpression of CKIs has been found to result in a specific block to entering mitosis while allowing progression through S-phase; consequently, weak misexpression plants displayed enhanced levels of endoreplication (Verkest et al, 2005a;Weinl et al, 2005). ICK/KRPs are largely believed to block CDKA;1 function, because in yeast two-hybrid interaction assays they strongly bind to A-type CDKs but no interaction of any of the ICK/KRPs to B-type CDKs has been reported Zhou et al, 2002).…”

“…Although plants possess two classes of CDK inhibitors (CKIs; the ICK/KRP and the SIM/EL2 classes), they show very little similarity with animal CDK inhibitors (Verkest et al, 2005b;Churchman et al, 2006;Wang et al, 2006). Furthermore, for the ICK/KRP class, it was found that at least one member can function in a non-cell-autonomous manner (Weinl et al, 2005).…”

Non-cell-autonomous rescue of anaphase-promoting complex function revealed by mosaic analysis of HOBBIT , an Arabidopsis CDC27 homolog

“…Might other cell cycle regulators, produced in cycling HBT cells as a consequence of ongoing cell division, move to hbt 2311 neighboring cells? In Arabidopsis, at least one putative cyclin-dependent kinase inhibitor, Kip-related protein1 (KRP1) (6,42) was recently shown to be capable of non-cell-autonomous action after ectopic expression (43). One possibility is that KRPs moving from actively dividing HBT cells counteract an excess of cyclin-dependent kinase͞cyclin B activity in hbt 2311 clones.…”

Eternal Youth, the Fate of Developing Arabidopsis Leaves uponRhodococcus fasciansInfection

“…CDKB1 is a plant-specific CDK dedicated to the G2-to-M transition (Boudolf et al, 2004b), whereas CDKA functions during both mitosis and the endocycle (Hemerly et al, 1995;Leiva-Neto et al, 2004;Verkest et al, 2005). Cell cycle exit and endoreduplication onset are accomplished through down-regulation of the mitotic CDK activity by inhibitors, such as KIP-related proteins (Wang et al, 1998;De Veylder et al, 2001;Verkest et al, 2005;Weinl et al, 2005;Nakai et al, 2006;Pettkó -Szandtner et al, 2006) and SIAMESE (SIM;Churchman et al, 2006). Other important control mechanisms for CDK activity are regulation of cyclin transcription and stability, and proteolysis by the anaphase-promoting complex-activating protein CELL CYCLE SWITCH52A (CCS52A; den Boer and Murray, 2000;Kondorosi and Kondorosi, 2004;Imai et al, 2006).…”