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Assays for the Degradation of Misfolded Proteins in Cells
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Published on: August 28, 2016

SIRT1 stabilizes PML promoting its sumoylation.

M Campagna1, D Herranz, M A Garcia

  • 1Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, Madrid 28049, Spain.

Cell Death and Differentiation
|June 26, 2010
PubMed
Summary
This summary is machine-generated.

Sirtuin 1 (SIRT1) protein deacetylase controls promyelocytic leukemia (PML) protein levels and PML nuclear bodies (PML-NBs). This regulation impacts viral infection responses and cellular apoptosis.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • Sirtuin 1 (SIRT1) is an NAD(+)-dependent deacetylase involved in cancer, aging, and metabolism.
  • SIRT1 localizes to the nucleus and is recruited to promyelocytic leukemia nuclear bodies (PML-NBs).
  • The specific functions of SIRT1 within PML-NBs remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the role of SIRT1 in regulating PML protein and PML-NBs.
  • To investigate the impact of SIRT1 on PML sumoylation and viral replication.

Main Methods:

  • Utilized primary mouse embryo fibroblasts and HEK-293 cells lacking or overexpressing SIRT1.
  • Employed knockdown strategies in HeLa cells to assess SIRT1's effect on PML.
  • Performed in vitro and in vivo experiments to analyze SIRT1's influence on PML sumoylation.
  • Assessed the apoptotic response and viral replication in SIRT1-deficient cells infected with vesicular stomatitis virus.

Main Results:

  • SIRT1 deficiency led to reduced PML protein levels, while SIRT1 reintroduction or overexpression increased PML levels.
  • Knockdown of SIRT1 decreased the size and number of PML-NBs and lowered PML protein levels.
  • SIRT1 was found to stimulate PML sumoylation in a deacetylase-independent manner.
  • Absence of SIRT1 impaired the apoptotic response to viral infection and enhanced viral replication.

Conclusions:

  • SIRT1 plays a novel and critical role in regulating PML protein expression and PML-NB formation.
  • SIRT1-mediated control of PML influences cellular responses to viral infections and apoptosis.