Related Experiment Video

Updated: Jun 25, 2026

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

MDM2 and MDM4 splicing: an integral part of the cancer spliceome

Selvi Jeyaraj1, Dennis M O'Brien, Dawn S Chandler

  • 1The Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.

Frontiers in Bioscience (Landmark Edition)
|March 11, 2009
PubMed

Insights

Murine double minute 2 (MDM2) and MDM4 proteins regulate tumor suppressor p53. Alternative splicing of MDM2 and MDM4 is linked to cancer, forming a cancer spliceome that aids in diagnosis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MDM2 and MDM4 are oncogenes regulating proteins, notably the tumor suppressor p53.
  • Precise p53 regulation is crucial for preventing malignancy and ensuring cell survival.
  • Alternative splicing of MDM2 and MDM4 is observed in various cancers.

Purpose of the Study:

  • To catalog alternatively spliced transcripts of MDM2 and MDM4.
  • To associate these splice variants with specific cancer types.
  • To understand the role of coordinated alternative splicing in cancer.

Main Methods:

  • Analysis of MDM2 and MDM4 gene transcripts.
  • Identification of alternative splicing events.
  • Correlation of splice variants with cancer patient data.

Main Results:

  • A comprehensive catalog of MDM2 and MDM4 alternatively spliced transcripts was generated.
  • Specific splice forms were linked to distinct cancer types.
  • UV irradiation was shown to induce alternative splicing in both MDM2 and MDM4.

Conclusions:

  • Coordinated alternative splicing of MDM2 and MDM4, termed the cancer spliceome, occurs in response to cellular stress and in cancerous cells.
  • This cancer spliceome provides a molecular fingerprint for aberrant cells.
  • Cataloging these splice variants aids in understanding cancer development and potential diagnostic markers.

More Related Videos

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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...
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 cells are...
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mismatch Repair01:36

Mismatch Repair

Overview