Related Experiment Video
Updated: May 14, 2026
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response
Joanna Bancerek1, Zachary C Poss, Iris Steinparzer
1Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
Immunity
|January 29, 2013
Summary
Cyclin-dependent kinase 8 (CDK8) phosphorylates Signal Transducer and Activator of Transcription (STAT) proteins, regulating gene expression and antiviral responses. This finding highlights CDK8 as a key regulator in cytokine signaling pathways.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Gene Regulation
Background:
- Signal transducer and activator of transcription (STAT) proteins are crucial for gene regulation by cytokines.
- Serine phosphorylation within the transactivation domain (TAD) is essential for STAT protein activity.
- The kinase responsible for STAT1 and STAT3 TAD phosphorylation remained unidentified.
Purpose of the Study:
- To identify the kinase responsible for STAT protein TAD phosphorylation.
- To investigate the role of this kinase in interferon (IFN) signaling and antiviral responses.
- To elucidate the impact of this phosphorylation on gene expression.
Main Methods:
- Utilized biochemical assays to identify kinase activity.
- Performed gene expression analysis using microarrays.
- Assessed RNA polymerase II occupancy at gene promoters.
- Investigated the role of CDK8 in IFN-γ-inducible antiviral responses.
Main Results:
- Identified the cyclin-dependent kinase 8 (CDK8) module of the Mediator complex as the kinase that phosphorylates STAT1, STAT3, and STAT5 TADs.
- Demonstrated CDK8's requirement for interferon-gamma (IFN-γ)-inducible antiviral responses.
- Showed that CDK8-mediated STAT1 phosphorylation regulates over 40% of IFN-γ-responsive genes, impacting both positive and negative gene expression.
- Observed correlation between RNA polymerase II occupancy and gene expression changes, irrespective of phosphorylation dependence.
Conclusions:
- CDK8 is a key regulator of STAT1 and antiviral responses.
- CDK8 plays a general role in STAT-mediated transcription.
- CDK8 represents a potential therapeutic target for modulating cytokine responses.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
02:34Inhibition 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...
02:34Inhibition 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...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...