Related Experiment Video

Updated: Jun 23, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

ZBTB2, a novel master regulator of the p53 pathway

Bu-Nam Jeon1, Won-Il Choi, Mi-Young Yu

  • 1Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Science, Institute of Genetic Science, Seoul 120-752, Korea.

The Journal of Biological Chemistry
|April 22, 2009
PubMed

Insights

ZBTB2, a transcription factor, represses the ARF-HDM2-p53-p21 pathway, particularly the cell cycle arrest gene p21. This repression impacts cell proliferation and suggests ZBTB2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The ARF-HDM2-p53-p21 pathway is crucial for cell cycle regulation.
  • Transcription factors play key roles in controlling gene expression within this pathway.

Purpose of the Study:

  • To investigate the role of ZBTB2, a POK family transcription factor, in regulating the ARF-HDM2-p53-p21 pathway.
  • To elucidate the molecular mechanisms by which ZBTB2 exerts its regulatory functions.

Main Methods:

  • Analysis of ZBTB2's effect on the transcription of ARF, HDM2, p53, and p21 genes.
  • Investigation of ZBTB2's interaction with transcription factors Sp1 and p53.
  • Examination of ZBTB2's interaction with corepressors (BCoR, NCoR, SMRT) and its effect on histone modifications.
  • Assessment of ZBTB2's impact on cell proliferation and DNA synthesis through ectopic expression and knockdown studies.

Main Results:

  • ZBTB2 acts as a potent repressor of the ARF-HDM2-p53-p21 pathway, repressing ARF, p53, and p21 transcription while activating HDM2.
  • ZBTB2 specifically represses p21 transcription by interfering with p53 and Sp1 binding to promoter elements.
  • ZBTB2 directly interacts with Sp1 and p53, inhibiting their transcriptional activity.
  • ZBTB2's POZ domain interacts with corepressors, leading to histone deacetylation and transcriptional repression.
  • ZBTB2 influences cell proliferation and DNA synthesis, with knockdown decreasing these processes.

Conclusions:

  • ZBTB2 is a potent transcription repressor of the cell cycle arrest gene p21.
  • ZBTB2 functions as a master control gene of the p53 pathway with potential proto-oncogenic activity.
  • ZBTB2's regulation of the p53 pathway has significant implications for cell cycle control and proliferation.

More Related Videos

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Related Concept Videos

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.
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...
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...
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.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...