Related Experiment Video

Updated: Sep 26, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Interferon regulatory factor-2 regulates cell growth through its acetylation

Atsuko Masumi1, Yoshio Yamakawa, Hidesuke Fukazawa

  • 1Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan. amasumi@nih.go.jp

The Journal of Biological Chemistry
|May 10, 2003
PubMed

Insights

Interferon regulatory factor-2 (IRF-2) acetylation at Lys-75 is crucial for histone H4 promoter activity in growing cells. This acetylation links IRF-2 to cell growth control.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Epigenetics

Background:

  • Interferon regulatory factor-2 (IRF-2) is known to be acetylated by p300 and PCAF.
  • Acetylation is a key post-translational modification regulating protein function.

Purpose of the Study:

  • To identify the specific acetylation sites on IRF-2.
  • To investigate the functional consequences of IRF-2 acetylation on DNA binding and transcriptional activity.
  • To determine the role of IRF-2 acetylation in cell growth regulation.

Main Methods:

  • Mass spectrometry to identify acetylation sites.
  • Site-directed mutagenesis to create acetylation-deficient IRF-2 mutants.
  • Reporter gene assays to measure promoter activity.
  • Chromatin immunoprecipitation (ChIP) assays to assess promoter binding in vivo.

Main Results:

  • Lys-75 and Lys-78 in the DNA binding domain (DBD) were identified as major IRF-2 acetylation sites.
  • Acetylation of IRF-2 did not affect in vitro DNA binding, but mutation of Lys-75 impaired IRF-2-dependent histone H4 promoter activation.
  • IRF-2 acetylation and H4 promoter activity were observed only in growing cells, not in growth-arrested cells.
  • Mutation of Lys-78 abolished DNA binding activity, independent of acetylation.
  • IRF-2 interacted with p300 and bound to the H4 promoter in growing cells, as shown by ChIP.

Conclusions:

  • IRF-2 acetylation occurs in a cell growth-dependent manner.
  • Lys-75 acetylation is essential for IRF-2's role in transcribing cell growth-regulated promoters, like histone H4.
  • These findings highlight the importance of IRF-2 post-translational modification in linking cell growth and transcriptional regulation.

More Related Videos

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.