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WDR74 functions as a novel coactivator in TGF-β signaling

Jinquan Liu1, Meiling Zhao2, Bo Yuan2

  • 1MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Journal of Genetics and Genomics = Yi Chuan Xue Bao
|December 31, 2018
PubMed

Insights

WD repeat-containing protein 74 (WDR74) acts as a novel coactivator for Smad proteins in transforming growth factor-beta (TGF-β) signaling. WDR74 enhances TGF-β responses by promoting Smad phosphorylation and nuclear entry, leading to stronger cellular signals.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Smad proteins are key mediators of transforming growth factor-beta (TGF-β) signaling pathways in mammalian cells.
  • Understanding the regulation of TGF-β signaling is crucial for various physiological processes and diseases.

Purpose of the Study:

  • To identify novel proteins that regulate the canonical TGF-β signaling pathway.
  • To investigate the role of WD repeat-containing protein 74 (WDR74) in TGF-β/Smad signaling.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Western blotting to assess protein phosphorylation and nuclear localization.
  • Reporter gene assays to measure transcriptional activity.

Main Results:

  • WD repeat-containing protein 74 (WDR74) directly interacts with Smad proteins.
  • WDR74 enhances TGF-β-induced phosphorylation and nuclear accumulation of Smad2 and Smad3.
  • WDR74 potentiates Smad-mediated transcriptional activation and TGF-β-induced physiological responses.

Conclusions:

  • WDR74 is a novel transcriptional coactivator in the canonical TGF-β signaling pathway.
  • WDR74 plays a critical role in amplifying TGF-β responses by modulating Smad activity.
  • These findings highlight WDR74 as a potential target for therapeutic interventions related to TGF-β signaling.
Keywords:
EMTGrowth inhibitionTGF-β signalingTranscriptionWDR74

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