Related Experiment Video
Updated: Jun 16, 2026
11:32
A Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) Platform for Investigating Peptide Biosynthetic Enzymes
Published on: May 4, 2020
Daxx is reciprocally regulated by Mdm2 and Hausp
Jun Tang1, Like Qu, Mingsu Pang
1State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan W. Rd., Haidian District, Beijing 100193, China. jtang@cau.edu.cn
Biochemical and Biophysical Research Communications
|February 16, 2010
Summary
Mdm2 (E3 ubiquitin ligase) and Hausp (de-ubiquitinase) regulate the multifunctional protein Daxx. Mdm2 ubiquitylates Daxx, reducing its expression, while Hausp de-ubiquitylates Daxx, controlling its cellular levels and stability.
Area of Science:
- Molecular and Cellular Biology
- Protein Regulation
- Ubiquitination and Deubiquitination Pathways
Background:
- Daxx is a crucial protein involved in apoptosis and transcription, but its regulatory mechanisms remain unclear.
- Previous research indicated a complex formation between Daxx, Mdm2 (E3 ubiquitin ligase), and Hausp (de-ubiquitinase).
Purpose of the Study:
- To elucidate the roles of Mdm2 and Hausp in the regulation of Daxx protein levels and function.
- To investigate the ubiquitination status of Daxx and its control by Mdm2 and Hausp.
Main Methods:
- In vitro and in vivo ubiquitination assays to assess Daxx modification by Mdm2.
- Over-expression studies to evaluate the impact of Mdm2 on Daxx expression.
- De-ubiquitination assays to determine Hausp's effect on Daxx stability.
Main Results:
- Daxx undergoes ubiquitination mediated by Mdm2 in both experimental systems.
- Mdm2 overexpression leads to a reduction in Daxx protein levels.
- Hausp plays a critical role in maintaining cellular Daxx levels, likely through de-ubiquitination.
Conclusions:
- Mdm2 and Hausp are key regulators of Daxx ubiquitination and protein stability.
- These findings provide new insights into the post-translational control of Daxx, impacting its diverse cellular functions.
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...
02:50Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
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...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:07MAPK 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...
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.