Biomaterial Database

RUNX3 Meets the Ubiquitin-Proteasome System in Cancer. 2023

Albano Toska, and Nikita Modi, and Lin-Feng Chen

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

RUNX3 is a transcription factor with regulatory roles in cell proliferation and development. While largely characterized as a tumor suppressor, RUNX3 can also be oncogenic in certain cancers. Many factors account for the tumor suppressor function of RUNX3, which is reflected by its ability to suppress cancer cell proliferation after expression-restoration, and its inactivation in cancer cells. Ubiquitination and proteasomal degradation represent a major mechanism for the inactivation of RUNX3 and the suppression of cancer cell proliferation. On the one hand, RUNX3 has been shown to facilitate the ubiquitination and proteasomal degradation of oncogenic proteins. On the other hand, RUNX3 can be inactivated through the ubiquitin-proteasome system. This review encapsulates two facets of RUNX3 in cancer: how RUNX3 suppresses cell proliferation by facilitating the ubiquitination and proteasomal degradation of oncogenic proteins, and how RUNX3 is degraded itself through interacting RNA-, protein-, and pathogen-mediated ubiquitination and proteasomal degradation.

UI	MeSH Term	Description	Entries
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D046988	Proteasome Endopeptidase Complex	A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.	20S Proteasome,Ingensin,Macropain,Macroxyproteinase,Multicatalytic Endopeptidase Complex,Multicatalytic Proteinase,Prosome,Proteasome,Complex, Multicatalytic Endopeptidase,Complex, Proteasome Endopeptidase,Endopeptidase Complex, Multicatalytic,Endopeptidase Complex, Proteasome,Proteasome, 20S,Proteinase, Multicatalytic
D050677	Core Binding Factor Alpha 3 Subunit	A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain.	AML2 Protein,Acute Myeloid Leukemia 2 Protein,CBFA3 Protein,Core-Binding Factor Alpha 3 Protein,PEBP2A3 Protein,Runt Domain Transcription Factor AML-2,Runt-Related Transcription Factor 3 Protein,Runx3 Protein,Core Binding Factor Alpha 3 Protein,Runt Related Transcription Factor 3 Protein
D054875	Ubiquitination	The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.	Ubiquitylation
D025801	Ubiquitin	A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.	APF-1,ATP-Dependent Proteolysis Factor 1,HMG-20,High Mobility Protein 20,Ubiquitin, Human,ATP Dependent Proteolysis Factor 1,Human Ubiquitin