Preferred Label : HOP Pathway;
NCIt synonyms : Homeodomain-Only Protein Pathway;
NCIt related terms : Hop Pathway in Cardiac Development;
Alternative definition : BIOCARTA: Homeodomain transcription factors comprise a large family of DNA binding
factors that regulate transcription and development. Many homeodomain genes arranged
in genomic clusters determine anterior-posterior patterning, while others determine
the fate of cells in specific tissues. The proliferation of cardiac myocytes and their
differentiation early in development are dependent on the coordinate expression and
action of serum response factor (SRF), GATA4 and the homeodomain factor Nkx2-5. All
three of these factors are expressed in developing cardiomyocytes and induce expression
of cardiac genes. Disruption of the Nkx2-5 gene in mice leads to embryonic lethality
and defective cardiac development. SRF also plays a dual role in cardiac development,
influencing both cardiomyocyte proliferation and differentiation depending on the
stage and other signals that are present. In addition, the Hop (Homeodomain Only Protein)
gene encodes a factor expressed early in cardiac development that is involved in cardiac
differentiation. Hop inactivation in vertebrates leads to severe defects in cardiac
development, acting downstream of Nkx2-5. Cardiac cells from mice lacking the Hop
gene fail to exit the cell cycle in the normal manner, continuing to proliferate past
the normal developmental stage. Many of the genes disregulated in the absence of Hop
are involved in the cell cycle and are also targets of SRF. Although Hop is a homeodomain
protein, it lacks a DNA-binding domain indicating that it must not regulate gene expression
directly. Hop appears to regulate the expression of cardiac genes by binding to SRF
and blocking DNA binding of SRF. The sequestration of SRF by Hop blocks the activation
of cardiac genes, preventing normal cardiac development. The influence of Hop on the
opposing processes of cardiomyocyte differentiation and proliferation reflect the
interaction of Hop with SRF and the duel role SRF plays. In early cardiac development,
Hop opposes differentiation induction by SRF, while at later stages Hop opposes the
proliferation induced by SRF. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_hopPathway;
Origin ID : C39107;
UMLS CUI : C1512315;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
