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<p>Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates cell proliferation, differentiation, migration, and apoptosis. It is generally accepted that TGF-β induces cellular responses through Smad-dependent gene transcription. However, the underlying mechanisms that modulate the transcriptional activities of Smads are not yet fully understood. Here, we identify BRD2, a member of the bromodomain and extraterminal (BET) family, as a key transcriptional coactivator for Smad3. BRD2 physically interacts with Smad3 through a newly identified Smad3-binding region (SBR). This BRD2-Smad interaction enhances Smad’s association with chromatin and amplifies its transcriptional activity, playing a vital role in TGF-β transcriptional and tumor-suppressive responses. Our findings establish BRD2 as an important modulator of TGF-β signaling and suggest that it may serve as a potential target for TGF-β-related diseases.</p>

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BRD2 is a transcriptional coactivator of Smad3 in mediating TGF-β tumor suppressive responses

  • 期刊论文

  • 发表日期：

    2026年4月15日

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  • Shuai Tian,
  • Shuchen Gu,
  • Shuangwu Sun,
  • Zhaoyang Wang,
  • Yingming Zhao,
  • Bo Yuan,
  • Xia Liu,
  • Bin Zhao,
  • Pinglong Xu,
  • Jin Cao,
  • Mu Xiao,
  • Yi Yu,
  • Xin-Hua Feng

摘要

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates cell proliferation, differentiation, migration, and apoptosis. It is generally accepted that TGF-β induces cellular responses through Smad-dependent gene transcription. However, the underlying mechanisms that modulate the transcriptional activities of Smads are not yet fully understood. Here, we identify BRD2, a member of the bromodomain and extraterminal (BET) family, as a key transcriptional coactivator for Smad3. BRD2 physically interacts with Smad3 through a newly identified Smad3-binding region (SBR). This BRD2-Smad interaction enhances Smad’s association with chromatin and amplifies its transcriptional activity, playing a vital role in TGF-β transcriptional and tumor-suppressive responses. Our findings establish BRD2 as an important modulator of TGF-β signaling and suggest that it may serve as a potential target for TGF-β-related diseases.