CREB-Regulated Transcriptional Coactivator 2 Proteome Landscape is Modulated by SREBF1

Jae Min Lim, Muhammad Ayaz Anwar, Hye Sook Han, Seung Hoi Koo, Kwang Pyo Kim

Research output: Contribution to journalArticlepeer-review

Abstract

cAMP response element-binding protein (CREB) regulated transcriptional coactivator 2 (CRTC2) is a critical transcription factor that maintains glucose homeostasis by activating CREB. Energy homeostasis is maintained through multiple pathways; therefore, CRTC2 may interact with other transcription factors, particularly under metabolic stress. CRTC2 liver-specific KO mice were created, and the global proteome, phosphoproteome, and acetylome from liver tissue under high-fat diet conditions were analyzed using liquid chromatography-tandem mass spectrometry and bioinformatics analysis. Differentially regulated proteins (DRPs) were enriched in metabolic pathways, which were subsequently corroborated through animal experiments. The consensus DRPs from these datasets were used as seed proteins to generate a protein-protein interaction network using STRING, and GeneMANIA identified fatty acid synthase as a mutually relevant protein. In an additional local-protein-protein interaction analysis of CRTC2 and fatty acid synthase with DRPs, sterol regulatory element binding transcription factor 1 (SREBF1) was the common mediator. CRTC2-CREB and SREBF1 are transcription factors, and DNA-binding motif analysis showed that multiple CRTC2-CREB–regulated genes possess SREBF1-binding motifs. This indicates the possible induction by the CRTC2–SREBF1 complex, which is validated through luciferase assay. Therefore, the CRTC2–SREBF1 complex potentially modulates the transcription of multiple proteins that fine-tune cellular metabolism under metabolic stress.

Original languageEnglish
Article number100637
JournalMolecular and Cellular Proteomics
Volume22
Issue number10
DOIs
Publication statusPublished - 2023 Oct

Bibliographical note

Publisher Copyright:
© 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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