PIWIL2 Suppresses Siah2-mediated Degradation of HDAC3 and Facilitates CK2α-mediated HDAC3 Phosphorylation

Cell Death Dis. 2018 Apr 1;9(4):423. doi: 10.1038/s41419-018-0462-8.


HDAC3 is involved in deacetylation of histone and non-histone proteins, having a key role in the regulation of gene transcription and also in the process of tumorgenesis. However, how HDAC3 is regulated in cancer remains largely unclear. Here, we showed that PIWIL2 can interact with HDAC3, leading to stabilization of HDAC3 from ubiquitin-mediated degradation by competitive association with E3 ubiquitin ligase Siah2. Furthermore, we found that expression of PIWIL2 enhanced HDAC3 activity via CK2α. PIWIL2 facilitated the interaction between HDAC3 and CK2α, thus exhibiting a promotion on the HDAC3 phosphorylation by CK2α. Further work showed that PIWIL2 could promote cell proliferation and suppress cell apoptosis via regulating HDAC3. Our present study firstly revealed that PIWIL2 can play a role in HDAC3-mediated epigenetic regulation on cancer cell proliferation and apoptosis. These findings provide a novel insight into the roles of PIWIL2 in tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology
  • Apoptosis
  • Argonaute Proteins / antagonists & inhibitors
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Cell Line, Tumor
  • Female
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Leupeptins / pharmacology
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Proteolysis / drug effects
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Ubiquitin-Protein Ligases / immunology
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology


  • Antibodies
  • Argonaute Proteins
  • Leupeptins
  • Nuclear Proteins
  • PIWIL2 protein, human
  • RNA, Small Interfering
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • CSNK2A1 protein, human
  • Casein Kinase II
  • Histone Deacetylases
  • histone deacetylase 3
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde