Novel interaction between nuclear coactivator CBP and the protein inhibitor of activated Stat1 (PIAS1)

Xiaolong Yin1, Dennis R Warner, Emily A Roberts

  • 1University of Louisville Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40292, USA.

Insights

Protein inhibitor of activated Stat1 (PIAS1) binds to cAMP response element binding protein (CREB)-binding protein (CBP). PIAS1 inhibits CBP

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Gene Regulation

Background:

  • cAMP response element binding protein (CREB)-binding protein (CBP) is a key transcriptional coactivator involved in gene regulation.
  • CBP expression is developmentally regulated in murine embryonic orofacial tissues, suggesting a role in development.

Purpose of the Study:

  • To identify novel nuclear factors interacting with CBP in developing embryonic orofacial tissue.
  • To investigate the functional consequences of CBP-interacting proteins on CBP's transcriptional activity.

Main Methods:

  • Yeast two-hybrid screening using the carboxy-terminal region of CBP as bait.
  • Glutathione S-transferase (GST) pull-down assays for in vitro binding confirmation.
  • Coimmunoprecipitation for in vivo interaction validation.
  • Reporter assays to assess effects on CBP-mediated transcription.

Main Results:

  • Protein inhibitor of activated Stat1 (PIAS1) was identified as a novel CBP-binding protein.
  • The interaction between PIAS1 and CBP was confirmed through both in vitro and in vivo methods.
  • PIAS1 was found to inhibit CBP-mediated transcriptional activation, independent of transforming growth factor-beta (TGF-β).

Conclusions:

  • PIAS1 is a novel binding partner for CBP.
  • PIAS1 acts as an inhibitor of CBP-mediated transcription.
  • These findings suggest PIAS1 may regulate embryonic development processes like cell proliferation, migration, and differentiation.

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