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Maf1 regulation: a model of signal transduction inside the nucleus

Yuehua Wei1, Xf Steven Zheng

  • 1Department of Pharmacology and Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Nucleus (Austin, Tex.)
|February 18, 2011
PubMed

Insights

The target of rapamycin complex 1 (TORC1) pathway regulates RNA polymerase III (Pol III) activity via the Maf1 repressor. Extracellular signals control Maf1 nuclear transport and phosphorylation, impacting Pol III transcription and cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • RNA polymerase III (Pol III) synthesizes essential RNAs (5S rRNA, tRNAs) for protein synthesis and cell growth.
  • Pol III activity is tightly regulated by growth signals; its deregulation is linked to oncogenic transformation.
  • The target of rapamycin complex 1 (TORC1) pathway, a key nutrient sensor, controls Pol III via the Maf1 repressor.

Purpose of the Study:

  • To elucidate the intricate mechanisms controlling Maf1 activity in response to extracellular stimuli.
  • To understand how nuclear transport and chromatin localization regulate Pol III-dependent transcription.
  • To highlight an emerging paradigm of nuclear gene regulation by extracellular signals.

Main Methods:

  • Investigated Maf1 regulation at multiple levels, including nuclear import/export.
  • Examined Maf1 phosphorylation dynamics at specific chromatin sites.
  • Analyzed the impact of these regulatory events on Pol III transcription.

Main Results:

  • Maf1 activity is controlled through sophisticated mechanisms involving its subcellular localization.
  • Phosphorylation of Maf1 at specific chromatin loci is a critical regulatory step.
  • These findings reveal a direct link between extracellular signals and nuclear gene expression control.

Conclusions:

  • Extracellular signals modulate Pol III transcription through Maf1 regulation within the nucleus.
  • Maf1's nuclear transport and phosphorylation are key integration points for growth signals.
  • This study reveals a novel mode of gene regulation impacting cell growth and potentially cancer development.
Keywords:
Maf1RNA polymerase IIInucleolusribosomal DNA (rDNA)target of rapamycin (TOR)transfer RNA (tRNA)

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