Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2011-5-12
pubmed:abstractText
Initiation of centrosome duplication and DNA replication is coupled, which is primarily achieved by the late G1 phase-specific activation of cyclin-dependent kinase 2 (CDK2)-cyclin E, which triggers both centrosome duplication and DNA replication. Uncoupling of these two events contributes to overduplication of centrosomes, resulting in the presence of more than two centrosomes (centrosome amplification). Centrosome amplification, which is frequently observed in cancers, contributes to tumor development through destabilizing genomes. Nucleophosmin (NPM/B23) is one of the phosphorylation targets of CDK2-cyclin E for the initiation of centrosome duplication. It has been found that NPM/B23 phosphorylated on Thr199 by CDK2-cyclin E acquires a high binding affinity to ROCK II kinase. The Thr199-phosphorylated NPM/B23 physically interacts with and super-activates the centrosomally localized ROCK II, which is a critical event for centrosomes to initiate duplication. Here, we provide direct evidence for the activation of ROCK II as a primary and sufficient downstream event of CDK2-cyclin E for the initiation of centrosome duplication and for the induction of centrosome amplification.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2188-97
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Activated ROCK II by-passes the requirement of the CDK2 activity for centrosome duplication and amplification.
pubmed:affiliation
Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9416, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural