High impact information on cki-1

• Genetic interaction and transgene expression studies suggest that cdc-14 functions upstream of the cki-1 Cip/Kip inhibitor to promote accumulation of CKI-1 in the nucleus [1].
• Loss of rnt-1 is correlated with upregulation of cki-1, a CDK inhibitor [2].
• Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine [3].
• lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C. elegans [4].
• We suggest that a rate limiting role for cki-1 Cip/Kip rather than lin-35 Rb explains the lack of cell-cycle phenotype of lin-35 mutant animals [4].

Biological context of cki-1

• Our findings demonstrate that cki-1 activity plays an essential role in embryonic cell cycle arrest, differentiation and morphogenesis, and suggest that it may be required to suppress programmed cell death or engulfment of cell corpses [5].
• cki-1 links cell division and cell fate acquisition in the C. elegans somatic gonad [6].
• Results from our laser microsurgery experiments suggest that the extra DTCs are caused by aberrant somatic gonadal precursor cell divisions in the absence of cki-1, resulting in abnormal daughter cell fates. cki-1(RNAi) animals also possess extra anchor cells and ectopic gonad arms with variable sheath cell numbers and positioning [6].
• Surprisingly, loss of cki-1, but not lin-35, results in precocious entry into S phase [4].
• Essential embryonic roles of the CKI-1 cyclin-dependent kinase inhibitor in cell-cycle exit and morphogenesis in C elegans [5].

Anatomical context of cki-1

• In vulva precursor cells (VPCs), a pathway of heterochronic genes acts via cki-1 to maintain VPCs in G1 during the L2 stage [7].
• We show that DAF-16 is required for transcription of the cyclin-dependent kinase inhibitor cki-1 in stem cells in response to starvation, accounting for the failure of daf-16/FOXO mutants to arrest cell division during L1 arrest [8].
• These include defects in mitotic chromosomal condensation and segregation, pronuclear rotation, and germ cell proliferation, abnormal cortical protrusion, and accumulation of the cyclin-dependent kinase inhibitor CKI1 [9].

Associations of cki-1 with chemical compounds

• ClC-2 currents attenuated by p34(cdc2)/cyclin B were increased by application of the cyclin-dependent kinase inhibitor, olomoucine (100 microM), an effect that was inhibited by calyculin A (5 nM) but not by okadaic acid (5 nM) [10].

Other interactions of cki-1

• C. elegans cki-1 encodes a member of the CIP/KIP family of cyclin-dependent kinase inhibitors, and functions to link postembryonic developmental programs to cell cycle progression [7].

References