Related Experiment Video

Updated: Jul 24, 2025

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

28.1K

RUNX3 inactivates oncogenic MYC through disruption of MYC/MAX complex and subsequent recruitment of GSK3β-FBXW7

Vincent Oei1,2, Linda Shyue Huey Chuang1, Junichi Matsuo1

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Communications Biology
|July 3, 2023
PubMed

Insights

Developmental regulator RUNX3 targets MYC protein for degradation via the GSK3β-FBXW7 pathway. This RUNX3-mediated MYC destabilization inhibits cancer development, offering new therapeutic insights.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • MYC is a frequently dysregulated proto-oncogene driving cancer initiation and progression.
  • MYC regulates critical cellular processes including proliferation and stem cell maintenance.

Purpose of the Study:

  • To elucidate the mechanism by which RUNX3 regulates MYC protein levels.
  • To investigate the role of RUNX3 in cancer development through MYC regulation.

Main Methods:

  • Investigated the interaction between RUNX3 and MYC.
  • Utilized the glycogen synthase kinase-3 beta-F-box/WD repeat-containing protein 7 (GSK3β-FBXW7) proteolytic pathway analysis.
  • Examined MYC protein phosphorylation and degradation via the ubiquitin-proteasomal pathway.
  • Assessed RUNX3's effect on cancer development in mouse models.

Main Results:

  • RUNX3 directly interacts with MYC via its Runt domain, disrupting MYC/MAX and MYC/MIZ-1 interactions.
  • RUNX3 promotes GSK3β-mediated phosphorylation of MYC at threonine-58.
  • This leads to enhanced ubiquitination and subsequent degradation of MYC protein.
  • RUNX3 inhibits early-stage cancer development in gastrointestinal and lung mouse models.

Conclusions:

  • RUNX3 destabilizes MYC protein through the GSK3β-FBXW7 pathway, representing a novel mechanism of MYC regulation.
  • RUNX3 acts as a tumor suppressor by targeting MYC, explaining its inhibitory effect on early cancer development.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:39

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

180
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

7.6K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.2K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.3K