# Context-specific Functions of CDK8

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $311,275

## Abstract

Title: Context-specific functions of CDK8
Project Summary:
The long-term goal of this project is to elucidate the function and regulation of the CDK8 module, a key
component of the transcription cofactor Mediator complex, in the versatile model organism Drosophila
melanogaster. The four subunits of the CDK8 module – CDK8, CycC, MED12, and MED13 – are either
mutated or amplified in cardiovascular diseases and a number of human cancers, such as melanoma and
colorectal cancers. Elucidating the function and regulation of the CDK8 module in different biological contexts
is essential to understanding the pathological consequences of CDK8 module misregulation, which is important
for the design of clinical strategies to treat these diseases. Studies in the previous funding cycle of this project
have demonstrated that CDK8-CycC serves as a critical regulatory node linking nutrient intake to fat
metabolism and developmental timing in Drosophila development. These studies have shown that CDK8-CycC
is a direct inhibitor of SREBP (sterol response element binding protein)-dependent gene expression, and that
CDK8-CycC positively regulates ecdysone receptor-activated gene expression. The overall objective of this
project is to unravel the function and regulation of CDK8 in different developmental contexts. Studies in the
previous funding cycle illustrate that Drosophila is an ideal and powerful experimental system to achieve this
long-term goal. Two new aims are proposed in this funding cycle. Aim 1 will determine the role of CDK8 in
regulating the expression of telomeric retrotransposons and telomere biology in Drosophila. Our RNA-seq
analyses revealed a specific upregulation of telomeric retrotransposon expression and a significant increase in
telomere length in cdk8 and cycC mutants. We have also discovered similar deregulation of telomeric
retrotransposon expression and telomere length in med7 and Scalloped (Sd) mutants. The transcription factor
Sd functions downstream of the conserved Hippo pathway. Thus we propose to examine the unexplored
functions of the CDK8 module and Sd in regulating the expression of telomeric retrotransposons and telomere
length in Drosophila. Aim 2 of the proposal will identify and validate upstream regulators and downstream
effectors of CDK8 in Drosophila. We have established novel and robust wing phenotypes caused by specific
alterations of CDK8 activities, allowing us to perform a dominant modifier genetic screen to identify factors
interacting with CDK8 in vivo. We have identified 26 genomic loci whose haploinsufficiency modifies these
CDK8-specific phenotypes; further genetic analysis led us to identify genetic interactions between CDK8 and
the components of the epidermal growth factor receptor (EGFR) and Dpp/TGFβ signaling pathways, as well as
several specific genes. In parallel, we have performed immunoprecipitation coupled to mass spectrometry (IP-
MS) analyses to identify proteins that can interact with CDK8. Combination o...

## Key facts

- **NIH application ID:** 10399883
- **Project number:** 7R01GM133011-08
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Jun-yuan Ji
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $311,275
- **Award type:** 7
- **Project period:** 2020-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399883

## Citation

> US National Institutes of Health, RePORTER application 10399883, Context-specific Functions of CDK8 (7R01GM133011-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399883. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*