Related Experiment Video

Updated: Jun 29, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism

D Mottet1, S Pirotte, V Lamour

  • 1Metastasis Research Laboratory, GIGA-Cancer (Center for Experimental Cancer Research), University of Liège, Liège, Belgium.

Oncogene
|October 14, 2008
PubMed

Insights

Histone deacetylase 4 (HDAC4) represses the p21(WAF1/Cip1) gene in cancer cells. Silencing HDAC4 reactivates p21(WAF1/Cip1), halting cancer and glioblastoma growth, suggesting HDAC4 as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Cancer cells exhibit uncontrolled proliferation and evade growth inhibition signals.
  • Global inhibition of histone deacetylases (HDACs) shows anti-cancer effects, partly via p21(WAF1/Cip1) gene reactivation.
  • Specific HDACs regulating p21(WAF1/Cip1) remain largely unidentified.

Purpose of the Study:

  • To identify the specific HDACs involved in p21(WAF1/Cip1) gene repression.
  • To investigate the role of HDAC4 in regulating p21(WAF1/Cip1) expression and its impact on cancer cell proliferation.
  • To evaluate HDAC4 as a potential therapeutic target for cancer treatment.

Main Methods:

  • Utilized small interfering RNAs (siRNAs) to silence HDAC4 expression.
  • Analyzed p21(WAF1/Cip1) gene regulation through Sp1/Sp3 and p53 binding sites.
  • Investigated HDAC4 interaction with Sp1 and its effect on histone acetylation at the p21(WAF1/Cip1) promoter.
  • Assessed the impact of HDAC4 silencing on cancer cell growth in vitro and tumor growth in a human glioblastoma xenograft model.

Main Results:

  • HDAC4 was found to repress p21(WAF1/Cip1) via Sp1/Sp3 binding sites, independent of p53.
  • HDAC4 interacts with Sp1 and reduces histone H3 acetylation at the p21(WAF1/Cip1) promoter.
  • Silencing HDAC4 led to p21(WAF1/Cip1) induction, inhibiting cancer cell proliferation in vitro.
  • HDAC4 inhibition suppressed tumor growth in an in vivo human glioblastoma model.

Conclusions:

  • HDAC4 plays a critical role in repressing the p21(WAF1/Cip1) gene in cancer.
  • HDAC4-mediated repression of p21(WAF1/Cip1) involves interaction with Sp1.
  • Targeting HDAC4 represents a promising strategy for novel anti-cancer therapies through selective HDAC inhibition.

More Related Videos

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique09:14

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique

Published on: January 14, 2016

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

Related Concept Videos

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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...