Proteomics

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CREB regulated transcriptional coactivator 2 proteome landscape is plausibly modulated by SREBF1


ABSTRACT: CRTC2 is a critical transcription cofactor that induces the glucose homeostatic genes by activating CREB. However, energy homeostasis is maintained by multiple pathways, therefore, it is possible that CRTC2 may interact with other transcription factors, especially under metabolic stress. Thereby, CRTC2 liver-specific knockout mice were created and the global proteome, phosphoproteome and acetylome from liver tissue under the high fat diet conditions were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. As expected, differentially expressed proteins (DEPs) are enriched in metabolic pathways that were subsequently corroborated by animal experiments. The consensus DEPs from these datasets were used as seed proteins to generate a protein-protein interaction (PPI) network using STRING and GeneMANIA identified fatty acid synthase (FASN) as the mutually relevant protein. Additional local-PPI (LPPI) analysis of CRTC2 and FASN with DEPs, SREBF1 was found to be a common mediator. CRTC2/CREB and SREBF1 are transcription factors, DNA-binding motif analysis showed multiple CRTC2/CREB regulated genes also possess SREBF1 binding motifs that unveil the possible induction by CRTC2/SREBF1 complex, which is reinforced by structural analysis. Thus, CRTC2/SREBF1 complex plausibly modulate the transcription of multiple proteins that fine-tune the cellular metabolism under metabolic stress.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Muhammad Ayaz Anwar  

LAB HEAD: Kwang Pyo Kim

PROVIDER: PXD039817 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

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

Lim Jae Min JM   Anwar Muhammad Ayaz MA   Han Hye-Sook HS   Koo Seung-Hoi SH   Kim Kwang Pyo KP  

Molecular & cellular proteomics : MCP 20230828 10


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 ana  ...[more]

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