H19 action Rb-E2F1 signaling and CDK-Beta-catenin activity (WP3969)

In this proposed model, H19 interacts with macroH2A, and this may consequently lead to de-repression of genes including CDK8, CDK4, and CCND1. Increased CDK4-cyclin D1 complex phosphorylates Rb to disrupt Rb-E2F1 interaction, leading to E2F1 activation. The increase of CDK8 expression enhances the function of mediator complex including MED1, and facilitates the gene regulation by β-catenin. These downstream targets could work in a synergistic way of promoting cell proliferation and increasing cell motility in CRC. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264449/ Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3969 CPTAC Assay Portal]
last edited


Khanspers and AlexanderPico

Cited In


Homo sapiens




Disease Ontology: colorectal cancer


Label Type Compact Identifier
macroH2A GeneProduct ensembl:ENSG00000113648
CDK4 GeneProduct ensembl:ENSG00000135446
H19 Rna ensembl:ENSG00000130600
G1-S transition Pathway wikipathways:WP45
CTNNB1 GeneProduct ensembl:ENSG00000168036
CCND1 GeneProduct ensembl:ENSG00000110092
E2F1 GeneProduct ensembl:ENSG00000101412
CDK8 GeneProduct ensembl:ENSG00000132964
CDK8 GeneProduct ensembl:ENSG00000132964
MED1 GeneProduct ensembl:ENSG00000125686
CSRP2 GeneProduct ensembl:ENSG00000175183
JAG1 GeneProduct ensembl:ENSG00000101384
SOX4 GeneProduct ensembl:ENSG00000124766
CDH1 GeneProduct ensembl:ENSG00000039068
TULP3 GeneProduct ensembl:ENSG00000078246
PMAIP1 GeneProduct ensembl:ENSG00000141682
RB1 GeneProduct ensembl:ENSG00000139687
E2F1 GeneProduct ensembl:ENSG00000101412
RB1 GeneProduct ensembl:ENSG00000139687


  1. Ohtsuka M, Ling H, Ivan C, Pichler M, Matsushita D, Goblirsch M, et al. H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer. EBioMedicine. 2016 Nov;13:113–24. PubMed Europe PMC Scholia