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

Homo sapiens

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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]

Authors

Kristina Hanspers , Alex Pico , and Egon Willighagen

Activity

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC

Annotations

Disease Ontology

colorectal cancer

Participants
Query Drugst.One

Label Type Compact Identifier Comment
macroH2A GeneProduct ensembl:ENSG00000113648
CDK4 GeneProduct ensembl:ENSG00000135446
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

References

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