The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell cycle quiescence during C. elegans development.
Cyclin-dependent kinase inhibitors (CKIs) are major contributors to the decision to enter or exit the cell cycle. The Caenorhabditis elegans genome encodes two CKIs belonging to the Cip/Kip family, cki-1 and cki-2. cki-1 has been shown to act as a canonical negative regulator of cell cycle entry, while the role of cki-2 remains unclear. We identified cki-2 in a genome-wide RNAi screen to reveal genes essential for developmental cell cycle quiescence. Examination of cki-2 knockout animals revealed extra rounds of cell divisions, verifying a role in establishing or maintaining the temporary cell cycle arrest. Despite the overlapping defects, the pathways mediated by cki-1 and cki-2 are discrete since the extra cell phenotype conferred by a putative cki-2(null) mutation is enhanced upon additional loss of cki-1 activity. Moreover, the extra cell division defect of cki-2 is not increased with the additional loss of lin-35 Rb, as is seen with cki-1. Thus, both cki-1 and cki-2 mediate cell cycle quiescence, but our genetic and phenotypic analyses demonstrate that they act within distinct pathways to exert control over the cell cycle machinery.
Buck
Sarah H
SH
Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
Chiu
Daniel
D
Saito
R Mako
RM
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial
D029742:Caenorhabditis elegans Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C042027:RNA I; D012329:RNA, Bacterial; C115024:cki-1 protein, C elegans; C412838:cki-2 protein, C elegans