Related Experiment Video
Updated: May 19, 2026
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
TRIAD1 is negatively regulated by the MDM2 E3 ligase
Seunghee Bae1, Jin Hyuk Jung, In-Sook An
1Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Oncology Reports
|September 4, 2012
Summary
The protein TRIAD1, which promotes apoptosis and p53 activation, is degraded by MDM2. This MDM2-mediated degradation of TRIAD1 (Two RING fingers and DRIL1) suppresses cancer cell growth.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein.
- TRIAD1 promotes p53 activation in various cancer cell lines.
- Understanding TRIAD1 regulation is crucial for cancer therapy.
Purpose of the Study:
- To investigate the regulatory mechanism of TRIAD1 protein.
- To identify proteins that ubiquitinate TRIAD1.
- To elucidate the role of TRIAD1 degradation in cancer cell growth.
Main Methods:
- Co-immunoprecipitation to study protein interactions.
- Western blotting to detect protein levels and ubiquitination.
- RNA interference to deplete MDM2 levels.
- Cell viability assays to assess cell growth.
Main Results:
- TRIAD1 interacts with and is ubiquitinated by murine double minute 2 (MDM2).
- MDM2 targets TRIAD1 for proteasome-dependent degradation.
- Knockdown of MDM2 enhances the stability of endogenous TRIAD1 protein.
- Degradation of TRIAD1 by MDM2 inhibits TRIAD1-mediated cell growth suppression.
Conclusions:
- MDM2 acts as an E3 ligase, ubiquinating TRIAD1 for degradation.
- This represents a novel negative regulatory pathway for TRIAD1.
- MDM2-mediated TRIAD1 degradation plays a role in suppressing cancer cell proliferation.
Related Concept Videos
02:23Abnormal 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 daughter...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:22PI3K/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 rapamycin-insensitive companion...
03:03mTOR 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...
The mTOR pathway or the...
02:17Separation of Sister Chromatids
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...