RPAP3 splicing variant isoform 1 interacts with PIH1D1 to compose R2TP complex for cell survival

Biochem Biophys Res Commun. 2013 Jan 4;430(1):320-4. doi: 10.1016/j.bbrc.2012.11.017. Epub 2012 Nov 15.


We previously characterized RNA polymerase II-associated protein 3 (RPAP3) as a cell death enhancer. Here we report the identification and characterization of splicing isoform of RPAP3, isoform 1 and 2. We investigated the interaction between RPAP3 and PIH1 domain containing protein 1 (PIH1D1), and found that RPAP3 isoform 1, but not isoform 2, interacted with PIH1D1. Furthermore, knockdown of RPAP3 isoform 1 by small interfering RNA down-regulated PIH1D1 protein level without affecting PIH1D1 mRNA. RPAP3 isoform 2 potentiated doxorubicin-induced cell death in human breast cancer T-47 cells although isoform 1 showed no effect. These results suggest that R2TP complex is composed of RPAP3 isoform 1 for its stabilization, and that RPAP3 isoform 2 may have a dominant negative effect on the survival potency of R2TP complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Survival
  • Down-Regulation
  • Doxorubicin / pharmacology
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism


  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • PIH1D1 protein, human
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Small Interfering
  • RPAP3 protein, human
  • Doxorubicin
  • TOR Serine-Threonine Kinases