PMID:25387524

Citation	Shen, ZJ, Hsu, PH, Su, YT, Yang, CW, Kao, L, Tseng, SF, Tsai, MD and Teng, SC (2014) PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase. Nat Commun 5:5312
Abstract	In yeast, the initiation of telomere replication at the late S phase involves in combined actions of kinases on Cdc13, the telomere binding protein. Cdc13 recruits telomerase to telomeres through its interaction with Est1, a component of telomerase. However, how cells terminate the function of telomerase at G2/M is still elusive. Here we show that the protein phosphatase 2A (PP2A) subunit Pph22 and the yeast Aurora kinase homologue Ipl1 coordinately inhibit telomerase at G2/M by dephosphorylating and phosphorylating the telomerase recruitment domain of Cdc13, respectively. While Pph22 removes Tel1/Mec1-mediated Cdc13 phosphorylation to reduce Cdc13-Est1 interaction, Ipl1-dependent Cdc13 phosphorylation elicits dissociation of Est1-TLC1, the template RNA component of telomerase. Failure of these regulations prevents telomerase from departing telomeres, causing perturbed telomere lengthening and prolonged M phase. Together our results demonstrate that differential and additive actions of PP2A and Aurora on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase.
Links	PubMed Online version:10.1038/ncomms6312
Keywords	Aurora Kinases/metabolism; Aurora Kinases/physiology; Cell Division/physiology; G2 Phase/physiology; Protein Phosphatase 2/metabolism; Protein Phosphatase 2/physiology; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae Proteins/physiology; Telomerase/metabolism; Telomerase/physiology; Telomere/metabolism; Telomere/physiology; Telomere-Binding Proteins/metabolism; Telomere-Binding Proteins/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:PP2A2	enables	GO:0004722: protein serine/threonine phosphatase activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(SGD:S000002379)	Seeded From UniProt	complete
YEAST:PP2A2	involved_in	GO:2000198: negative regulation of ribonucleoprotein complex localization	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(GO:0000781) happens_during:(GO:0000086)	Seeded From UniProt	complete
YEAST:CDC13	involved_in	GO:0071166: ribonucleoprotein complex localization	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(GO:0000624) happens_during:(GO:0000084) has_input:(GO:0005697)	Seeded From UniProt	complete
YEAST:IPL1	enables	GO:0004672: protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(SGD:S000002379)	Seeded From UniProt	complete
YEAST:IPL1	involved_in	GO:0018105: peptidyl-serine phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P	happens_during:(GO:0000086) has_direct_input:(UniProtKB:P32797)	Seeded From UniProt	complete
YEAST:IPL1	enables	GO:0004672: protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_direct_input:(UniProtKB:P32797)	Seeded From UniProt	complete

References

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