RGD Reference Report - Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin. - Rat Genome Database

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Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin.

Authors: Liu, ZP  Wang, Z  Yanagisawa, H  Olson, EN 
Citation: Liu ZP, etal., Dev Cell. 2005 Aug;9(2):261-70.
RGD ID: 10402362
Pubmed: PMID:16054032   (View Abstract at PubMed)
DOI: DOI:10.1016/j.devcel.2005.05.017   (Journal Full-text)

Smooth muscle cells (SMCs) modulate their phenotype between proliferative and differentiated states in response to physiological and pathological cues. Insulin-like growth factor-I stimulates differentiation of SMCs by activating phosphoinositide-3-kinase (PI3K)-Akt signaling. Foxo forkhead transcription factors act as downstream targets of Akt and are inactivated through phosphorylation by Akt. We show that Foxo4 represses SMC differentiation by interacting with and inhibiting the activity of myocardin, a transcriptional coactivator of smooth muscle genes. PI3K/Akt signaling promotes SMC differentiation, at least in part, by stimulating nuclear export of Foxo4, thereby releasing myocardin from its inhibitory influence. Accordingly, reduction of Foxo4 expression in SMCs by siRNA enhances myocardin activity and SMC differentiation. We conclude that signal-dependent interaction of Foxo4 with myocardin couples extracellular signals with the transcriptional program for SMC differentiation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neointima  ISOFoxo4 (Mus musculus)10402362; 10402362protein:increased expression:smooth muscle cell:RGD 
Neointima  IEP 10402362protein:increased expression:smooth muscle cell:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Foxo4  (forkhead box O4)
Myocd  (myocardin)

Genes (Mus musculus)
Foxo4  (forkhead box O4)

Genes (Homo sapiens)
FOXO4  (forkhead box O4)


Additional Information