Related Experiment Video

Updated: Aug 23, 2025

Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy
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Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy

Published on: May 28, 2021

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Cdk8 attenuates lipogenesis by inhibiting SREBP-dependent transcription in Drosophila

Xiao Li1, Meng Zhang2, Mengmeng Liu2

  • 1Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.

Disease Models & Mechanisms
|October 28, 2022
PubMed

Insights

CDK8 phosphorylation of SREBP transcription factors is crucial for regulating lipogenic gene expression. Preventing this phosphorylation enhances SREBP stability and lipogenesis, even during starvation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Lipid homeostasis relies on precise control of lipogenic gene expression.
  • Sterol regulatory element-binding proteins (SREBPs) are key transcription factors regulating lipid and cholesterol metabolism.
  • The precise mechanisms governing SREBP activity remain incompletely understood.

Purpose of the Study:

  • To investigate the role of CDK8-mediated phosphorylation in SREBP regulation.
  • To elucidate how SREBP phosphorylation affects lipogenic gene transcription and lipid homeostasis.
  • To identify the molecular interactions between SREBP, CDK8, and the Mediator complex.

Main Methods:

  • Utilized Drosophila melanogaster as a model system to study SREBP function.
  • Employed phosphodeficient SREBP mutants (SREBP-Thr390Ala) to assess the impact of phosphorylation.
  • Conducted biochemical analyses to map SREBP interaction domains with Cdk8 and MED15.

Main Results:

  • Phosphodeficient SREBP exhibited increased stability and enhanced lipogenic gene expression in vivo compared to wild-type.
  • Starvation inhibited wild-type SREBP-induced lipogenesis but not that of phosphodeficient SREBP.
  • Identified six conserved residues in SREBP's N-terminus essential for Cdk8 and MED15 binding.

Conclusions:

  • CDK8-mediated phosphorylation is a critical regulatory mechanism for SREBP activity.
  • The interaction with Cdk8 and MED15 is vital for the precise control of SREBP-dependent transcription.
  • These findings provide insights into the regulation of lipid metabolism and homeostasis.
Keywords:
DrosophilaCdk8LipogenesisMediator complexSREBP

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