Related Experiment Video

Updated: Mar 9, 2026

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

3.0K

Otub1 stabilizes MDMX and promotes its proapoptotic function at the mitochondria

Yingxiao Chen1, Yue-Gang Wang1, Yuhuang Li1

  • 1Department of Molecular and Medical Genetics, School of Medicine, and The OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.

Oncotarget
|December 31, 2016
PubMed

Insights

Otub1 stabilizes MDMX protein, enhancing its mitochondrial localization and promoting p53 phosphorylation at S46. This pathway is crucial for apoptosis induction, particularly after UV irradiation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Otub1 is known to regulate p53 stability by inhibiting UbcH5, a ubiquitin-conjugating enzyme crucial for MDM2.
  • The effect of Otub1 on MDMX stability and function remained unclear.

Purpose of the Study:

  • To investigate whether Otub1 regulates MDMX stability and activity.
  • To elucidate the role of Otub1-mediated MDMX regulation in p53 activation and apoptosis.

Main Methods:

  • Cell-based assays to assess MDMX ubiquitination and stability.
  • In vitro ubiquitination assays.
  • Mitochondrial localization studies of MDMX.
  • Analysis of p53 phosphorylation at S46 (p53S46P) and apoptosis induction.
  • UV irradiation experiments to study apoptosis pathways.

Main Results:

  • Otub1 suppresses MDM2-mediated MDMX ubiquitination, independent of its deubiquitinating activity.
  • Otub1 overexpression stabilizes MDMX, increasing its cellular levels.
  • Otub1-induced MDMX localizes to mitochondria, enhancing p53S46P and promoting apoptosis.
  • Knockdown of MDMX diminishes Otub1-induced p53S46P and apoptosis.
  • Otub1 promotes UV-induced p53S46P and apoptosis, which is inhibited by MDMX depletion.

Conclusions:

  • Otub1 stabilizes MDMX, contributing to p53S46P and mitochondria-mediated apoptosis.
  • This represents an alternative mechanism for Otub1's role in apoptosis induction.
Keywords:
MDMXOtub1apoptosisdeubiquitinating enzymesp53

More Related Videos

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

3.3K
Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue09:27

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

40.8K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.0K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.6K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
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...
5.3K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.1K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.8K