Related Experiment Video

Updated: Jan 29, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

8.9K

Protein phosphatase PPP3CA (calcineurin A) down-regulates hypoxia-inducible factor transcriptional activity

Angeliki Karagiota1, Ilias Mylonis1, George Simos2

  • 1Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece.

Archives of Biochemistry and Biophysics
|February 19, 2019
PubMed

Insights

The serine-threonine phosphatase PPP3CA (calcineurin A) negatively regulates hypoxia-inducible factor (HIF) activity. Silencing PPP3CA enhances HIF activity, revealing its role in fine-tuning the cellular response to low oxygen conditions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Hypoxia-inducible factors (HIFs) are crucial for cellular adaptation to low oxygen.
  • While kinases are known regulators of HIFs, the role of phosphatases remains largely unexplored.
  • Understanding phosphatase involvement is key to fully elucidating HIF regulation.

Purpose of the Study:

  • To identify phosphatases that regulate HIF transcriptional activity.
  • To investigate the specific role of PPP3CA (calcineurin A) in HIF control.
  • To elucidate the mechanism by which PPP3CA influences HIF-dependent gene expression.

Main Methods:

  • Screening a library of siRNAs targeting human phosphatase catalytic subunits in HeLa cells.
  • Assessing the impact of phosphatase silencing on HIF transcriptional activity under hypoxic conditions.
  • Utilizing gene silencing, overexpression of PPP3CA variants, and ionomycin treatment to study PPP3CA function.

Main Results:

  • PPP3CA was identified as a significant negative regulator of HIF activity.
  • Silencing PPP3CA expression increased HIF transcriptional activity without altering HIF-α protein levels.
  • Active PPP3CA inhibited HIF activity and target gene expression, an effect mimicked and enhanced by ionomycin.

Conclusions:

  • PPP3CA plays a critical role in negatively regulating HIF transcriptional activity.
  • PPP3CA fine-tunes the HIF-dependent transcriptional response to hypoxia.
  • This study highlights phosphatases as important modulators of the cellular oxygen-sensing pathway.
Keywords:
CalcineurinHIF-1HIF-2HypoxiaPPP3CA

More Related Videos

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

807
Rapid Synthesis and Screening of Chemically Activated Transcription Factors with GFP-based Reporters09:22

Rapid Synthesis and Screening of Chemically Activated Transcription Factors with GFP-based Reporters

Published on: November 26, 2013

15.0K

Related Concept Videos

Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.7K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.1K
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...
7.8K
Transcription Elongation Factors02:35

Transcription Elongation Factors

Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
13.8K
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.8K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.3K