Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity

Indra Tumurbaatar, Onur Cizmecioglu, Ingrid Hoffmann, Ingrid Grummt, Renate Voit

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.

Original languageEnglish (US)
Article numbere14711
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - Feb 28 2011

Fingerprint

Cyclin B
Phosphorylation
cyclins
Chromosomes
Mitosis
Yeast
mitosis
cdc25 Phosphatases
Phosphoric Monoester Hydrolases
Chemical activation
Modulation
dephosphorylation
Defects
Substrates
phosphorylation
Yeasts
yeasts
Chromosome Segregation
Anaphase
chromosome segregation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity. / Tumurbaatar, Indra; Cizmecioglu, Onur; Hoffmann, Ingrid; Grummt, Ingrid; Voit, Renate.

In: PloS one, Vol. 6, No. 2, e14711, 28.02.2011.

Research output: Contribution to journalArticle

Tumurbaatar, Indra ; Cizmecioglu, Onur ; Hoffmann, Ingrid ; Grummt, Ingrid ; Voit, Renate. / Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity. In: PloS one. 2011 ; Vol. 6, No. 2.
@article{decbc2c4fe144b46a6d11794adb3708d,
title = "Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity",
abstract = "Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.",
author = "Indra Tumurbaatar and Onur Cizmecioglu and Ingrid Hoffmann and Ingrid Grummt and Renate Voit",
year = "2011",
month = "2",
day = "28",
doi = "10.1371/journal.pone.0014711",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity

AU - Tumurbaatar, Indra

AU - Cizmecioglu, Onur

AU - Hoffmann, Ingrid

AU - Grummt, Ingrid

AU - Voit, Renate

PY - 2011/2/28

Y1 - 2011/2/28

N2 - Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.

AB - Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.

UR - http://www.scopus.com/inward/record.url?scp=79951859251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951859251&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0014711

DO - 10.1371/journal.pone.0014711

M3 - Article

C2 - 21379580

AN - SCOPUS:79951859251

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e14711

ER -