Related Experiment Video

Updated: Jun 20, 2026

Assessing Functional Performance in the Mdx Mouse Model
10:32

Assessing Functional Performance in the Mdx Mouse Model

Published on: March 27, 2014

MDM4 (MDMX) and its Transcript Variants

F Mancini1, G Di Conza, F Moretti

  • 1National Council of Research, Institute of Neurobiology and Molecular Medicine, Roma.

Current Genomics
|September 2, 2009
PubMed

Insights

MDM4 (MDM family member 4) splicing variants fine-tune wild-type protein function in normal cells but can promote oncogenesis in tumors. This review details MDM4 variants, their structures, and interactions, comparing them to MDM2 variants.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • MDM family proteins regulate the oncosuppressor p53, with gene alterations frequently observed in human tumors.
  • MDM4, a member of the MDM family, is encoded by a gene on chromosome 1 and exists as a full-length protein and various transcript variants.
  • These MDM4 variants arise from canonical and aberrant splicing, with some found in normal tissues and others exclusively in tumors.

Purpose of the Study:

  • To review all described MDM4 splicing forms and their regulatory roles on wild-type MDM4 function in both normal and tumor cells.
  • To present the structure of full-length MDM4 protein, its interacting partners, and compare the structures of MDM4 variants to the full-length protein.
  • To discuss the parallels between MDM4 and MDM2 variants in cancer biology.

Main Methods:

  • Literature review of studies describing MDM4 splicing variants.
  • Analysis of protein structure and interactions of full-length MDM4.
  • Comparative analysis of MDM4 and MDM2 variants.

Main Results:

  • MDM4 variants are generated through splicing, including aberrant events, and exhibit differential expression in normal versus tumor tissues.
  • Some MDM4 variants modulate the function of the full-length protein in normal cells, while others possess oncogenic properties in tumor cells.
  • The review provides a comprehensive overview of MDM4 variant structures, interactions, and functional implications.

Conclusions:

  • MDM4 splicing variants play a significant role in regulating p53 pathway activity, impacting both normal cellular functions and tumor development.
  • Understanding MDM4 variants is crucial for comprehending cancer mechanisms and potentially developing targeted therapies.
  • The comparison with MDM2 variants highlights conserved and distinct roles of MDM family members in cancer.
Keywords:
MDM2.MDM4MDM4-211MDM4-Sp53transcript variants

More Related Videos

Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy10:30

Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy

Published on: May 24, 2016

CD Spectroscopy to Study DNA-Protein Interactions06:48

CD Spectroscopy to Study DNA-Protein Interactions

Published on: February 10, 2022

Related Concept Videos

Master Transcription Regulators02:23

Master 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...
Master Transcription Regulators02:23

Master 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...
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 daughter...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...