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PMID:25387524

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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

Significance

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

Seeded From UniProt

complete

YEAST:CDC13

involved_in

GO:0071166: ribonucleoprotein complex localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

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

Notes

See also

References

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