Linked Life Data

21757741

Source:http://linkedlifedata.com/resource/pubmed/id/21757741

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2011-8-22
pubmed:abstractText
PTTG1, also known as securin, is an inactivating partner of separase, the major effector for chromosome segregation during mitosis. At the metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome, allowing activation of separase. In addition, securin is overexpressed in metastatic or genomically instable tumors, suggesting a relevant role for securin in tumor progression. Stability of securin is regulated by phosphorylation; some phosphorylated forms are degraded out of mitosis, by the action of the SKP1-CUL1-F-box protein (SCF) complex. The kinases targeting securin for proteolysis have not been identified, and mechanistic insight into the cause of securin accumulation in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3? (GSK3?) phosphorylates securin to promote its proteolysis via SCF(?TrCP) E3 ubiquitin ligase. Importantly, a strong correlation between securin accumulation and GSK3? inactivation was observed in breast cancer tissues, indicating that GSK3? inactivation may account for securin accumulation in breast cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30047-56
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Glycogen synthase kinase-3beta (GSK3beta) negatively regulates PTTG1/human securin protein stability, and GSK3beta inactivation correlates with securin accumulation in breast tumors.
pubmed:affiliation
Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't