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YAF2 exerts anti-apoptotic effect in human tumor cells in a FANK1- and phosphorylation-dependent manner

Shiqiang Zhang1, Xuan Zhang2, Xin Guan3

  • 1Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.

Biochemical and Biophysical Research Communications
|March 30, 2021
PubMed

Insights

Phosphorylated YY1-associated factor 2 (YAF2) prevents cancer cell death by stabilizing fibronectin type III and ankyrin repeat domains 1 (FANK1) protein levels, inhibiting apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • YY1-associated factor 2 (YAF2) is known to regulate gene transcription via epigenetic and non-epigenetic pathways.
  • The full spectrum of YAF2's biological functions and regulatory mechanisms remains incompletely understood.

Purpose of the Study:

  • To investigate novel mechanisms by which YAF2 influences cellular processes, specifically focusing on its role in human tumor cells.
  • To elucidate the function of phosphorylated YAF2 and its interaction with fibronectin type III and ankyrin repeat domains 1 (FANK1).

Main Methods:

  • Analysis of YAF2 phosphorylation status in human tumor and non-tumor cells.
  • Investigation of the effect of phosphorylated YAF2 on FANK1 protein levels using siRNA-mediated knockdown.
  • Examination of the interaction between YAF2 and FANK1, including binding domains.
  • Assessment of the impact of phosphorylated YAF2 on tumor cell apoptosis in a FANK1-dependent manner.

Main Results:

  • YAF2 is predominantly expressed as a Serine 167 phosphorylated form in human cells.
  • Phosphorylated YAF2 enhances FANK1 protein stability by inhibiting its proteasomal degradation.
  • The FN3 domain of FANK1 interacts with the N-terminal region of YAF2.
  • Phosphorylated YAF2 demonstrates anti-apoptotic activity in tumor cells, mediated by FANK1.

Conclusions:

  • Phosphorylated YAF2 plays a critical role in regulating FANK1 protein stability.
  • YAF2's anti-apoptotic function in cancer cells is mediated through its interaction with FANK1.
  • This study reveals a novel mechanism of YAF2-mediated tumor cell survival.
Keywords:
ApoptosisFANK1PhosphorylationProtein interactionYAF2

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