Linked Life Data

20019746

Source:http://linkedlifedata.com/resource/pubmed/id/20019746

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-10
pubmed:abstractText
Paired-like homeodomain 2 (Pitx2), first identified as the gene responsible for the Axenfeld-Rieger syndrome, encodes a protein factor that, controlling cell proliferation in a tissue-specific manner, has a crucial role in morphogenesis. During embryonic development, Pitx2 exerts a role in the expansion of muscle progenitors and is expressed at all stages of myogenic progression. In this study, we show that Pitx2 is phosphorylated by the protein kinase Akt2 and is necessary to ensure proper C2C12 myoblast proliferation and differentiation. Pitx2 associates with a ribonucleoprotein complex that includes the mRNA stabilizing factor HuR and sustains Ccnd1 (also known as Cyclin D1) expression, thereby prolonging its mRNA half-life. When the differentiation program is initiated, phosphorylation by Akt2 impairs the ability of Pitx2 to associate with the Ccnd1 mRNA-stabilizing complex that includes HuR and, as a consequence, Ccnd1 mRNA half-life is shortened. We propose that unphosphorylated Pitx2 is required to favor HuR-mediated Ccnd1 mRNA stabilization, thus sustaining myoblast proliferation. Upon Akt2-phosphorylation, the complex Pitx2/HuR/Ccnd1 mRNA dissociates and Ccnd1 mRNA is destabilized. These events contribute to the switch of C2C12 cells from a proliferating to a differentiating phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
975-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay during muscle cell differentiation.
pubmed:affiliation
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. rgherzi@ucsd.edu <rgherzi@ucsd.edu>
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't