Nucleophosmin Interacts with PIN2/TERF1-interacting Telomerase Inhibitor 1 (PinX1) and Attenuates the PinX1 Inhibition on Telomerase Activity

Sci Rep. 2017 Mar 3:7:43650. doi: 10.1038/srep43650.

Abstract

Telomerase activation and telomere maintenance are critical for cellular immortalization and transformation. PIN2/TERF1-interacting telomerase inhibitor 1 (PinX1) is a telomerase regulator and the aberrant expression of PinX1 causes telomere shortening. Identifying PinX1-interacting proteins is important for understanding telomere maintenance. We found that PinX1 directly interacts with nucleophosmin (NPM), a protein that has been shown to positively correlate with telomerase activity. We further showed that PinX1 acts as a linker in the association between NPM and hTERT, the catalytic subunit of telomerase. Additionally, the recruitment of NPM by PinX1 to the telomerase complex could partially attenuate the PinX1-mediated inhibition on telomerase activity. Taken together, our data reveal a novel mechanism that regulates telomerase activation through the interaction between NPM, PinX1 and the telomerase complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins
  • Cell Line
  • Enzyme Activation
  • Humans
  • Multiprotein Complexes
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Telomerase / antagonists & inhibitors
  • Telomerase / chemistry
  • Telomerase / metabolism*
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Multiprotein Complexes
  • NPM1 protein, human
  • Nuclear Proteins
  • PINX1 protein, human
  • Tumor Suppressor Proteins
  • Nucleophosmin
  • Telomerase