INMAP, a novel truncated version of POLR3B, represses AP-1 and p53 transcriptional activity

Mol Cell Biochem. 2013 Feb;374(1-2):81-9. doi: 10.1007/s11010-012-1507-4. Epub 2012 Nov 4.

Abstract

INMAP was first identified as an interphase nucleus and mitotic apparatus-associated protein that plays essential roles in the formation of the spindle and cell-cycle progression. Here, we report that INMAP might be conserved from prokaryotes to humans, is a truncated version of the RNA polymerase III subunit B POLR3B, and is up-regulated in several human cancer cell lines including HeLa, Bel-7402, HepG2 and BGC-823. Deletion analysis revealed that the 209-290 amino-acid region is necessary for the punctate distribution of INMAP in the nucleus. Furthermore, over-expression of INMAP inhibited the transcriptional activities of p53 and AP-1 in a dose-dependent manner. These results suggest that INMAP may function through the p53 and AP-1 pathways, thus providing a possible link of its activity with tumourigenesis. Integrating our data and those in previous studies, it can be concluded that INMAP plays dual functional roles in the coordination of mitotic kinetics with gene expression as well as in cell-fate determination and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Gene Expression
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Polymerase III / chemistry
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism*
  • Sequence Deletion
  • Transcription Factor AP-1 / biosynthesis
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cell Cycle Proteins
  • INMAP protein, human
  • Nuclear Proteins
  • Transcription Factor AP-1
  • Tumor Suppressor Protein p53
  • POLR3B protein, human
  • RNA Polymerase III