Related Experiment Video

Updated: Aug 8, 2026

Massively Parallel Reporter Assays in Cultured Mammalian Cells
11:03

Massively Parallel Reporter Assays in Cultured Mammalian Cells

Published on: August 17, 2014

Role of PML and PML-RARalpha in Mad-mediated transcriptional repression

M M Khan1, T Nomura, H Kim

  • 1Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 305-0074, Ibaraki, Japan.

Molecular Cell
|June 30, 2001
PubMed

Insights

The promyelocytic leukemia (PML) protein fused to retinoic acid receptor-alpha (RARalpha) drives leukemia. This study reveals PML-RARalpha disrupts normal PML function by interfering with corepressor complexes, potentially causing cancer.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Hematology

Background:

  • Acute promyelocytic leukemia (APL) is characterized by the PML-RARalpha fusion protein.
  • The precise mechanisms by which PML-RARalpha drives leukemogenesis are not fully understood.
  • The promyelocytic leukemia (PML) protein plays roles in apoptosis and transcriptional regulation.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying PML-RARalpha-mediated leukemogenesis.
  • To identify interactions between PML and corepressor complexes.
  • To determine how PML-RARalpha affects the function of PML and associated proteins.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Analysis of transcriptional repression mediated by the tumor suppressor Mad.
  • Investigating the role of corepressor-binding sites in PML-RARalpha function.

Main Results:

  • PML interacts with corepressors c-Ski, N-CoR, and mSin3A, along with histone deacetylase 1.
  • This interaction is crucial for Mad-mediated transcriptional repression.
  • PML-RARalpha possesses two corepressor-interacting sites and inhibits Mad-mediated repression.
  • Aberrant binding of PML-RARalpha to corepressor complexes abrogates their function.

Conclusions:

  • PML-RARalpha disrupts normal PML function by interfering with corepressor complexes.
  • This disruption of corepressor function by PML-RARalpha is a potential mechanism contributing to leukemogenesis in APL.
  • Targeting these aberrant interactions may offer therapeutic strategies for APL.

More Related Videos

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells06:48

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells

Published on: June 16, 2022

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...