YY1 Oligomerization Is Regulated by Its OPB Domain and Competes with Its Regulation of Oncoproteins

Shiyao Qiao1, Wenmeng Wang1, Cheng Yi1

  • 1College of Life Science, Northeast Forestry University, Harbin 150040, China.

Cancers
|April 12, 2022
PubMed

Insights

Yin Yang 1 (YY1) oligomerization is regulated by its oncoprotein binding (OPB) domain. Disrupting OPB interactions enhances YY1

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Yin Yang 1 (YY1) is an oncogenic transcription factor.
  • YY1 protein oligomerization has been observed but lacks clear biological significance.
  • The domains mediating YY1 intermolecular interactions were not well-defined.

Purpose of the Study:

  • To identify the domains responsible for YY1 intermolecular interactions.
  • To investigate the biological implications of YY1 oligomerization.
  • To explore the role of the oncoprotein binding (OPB) domain in YY1 function.

Main Methods:

  • Site-directed mutagenesis of YY1 domains, specifically the OPB domain.
  • Expression of wild-type and mutant YY1 in breast cancer cells with endogenous YY1 knockdown.
  • Assessment of cell proliferation and migration.
  • Analysis of protein-protein interactions, including with EZH2, AKT, and MDM2.

Main Results:

  • The oncoprotein binding (OPB) and zinc finger (ZF) domains are involved in YY1 intermolecular interactions.
  • Mutations in the OPB domain (YY1(F219A) and YY1(3A)) disrupted YY1 oligomerization.
  • The OPB peptide alone could promote YY1 oligomerization.
  • YY1 mutants defective in oligomerization exhibited enhanced promotion of breast cancer cell proliferation and migration.
  • Mutant YY1 showed altered interactions with EZH2, AKT, and MDM2, notably increased binding affinity for EZH2.

Conclusions:

  • The OPB domain is critical for YY1 oligomerization.
  • YY1 oligomerization plays a regulatory role in YY1's oncogenic functions.
  • There may be a mutually exclusive relationship between YY1-mediated enhancer formation and its promotion of oncoproteins.

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