Correlation Engine 2.0
Clear Search sequence regions

  • adp (3)
  • AICAR (1)
  • AMPK (2)
  • culture media (2)
  • culture media, serum- free (2)
  • cytoplasm (1)
  • cytosol (1)
  • embryo mammalian (1)
  • ex 527 (1)
  • fibroblasts (2)
  • free (2)
  • gene (2)
  • LC3 (4)
  • Map1lc3b (1)
  • mice (1)
  • myoblasts (2)
  • nad (4)
  • PARP1 (1)
  • PARP10 (1)
  • PARP2 (12)
  • proteolysis (1)
  • serum (3)
  • SIRT1 (3)
  • Sizes of these terms reflect their relevance to your search.

    Poly(ADP-Ribose) polymerases (PARPs) are enzymes that metabolize NAD+. PARP1 and PARP10 were previously implicated in the regulation of autophagy. Here we showed that cytosolic electron-dense particles appear in the cytoplasm of C2C12 myoblasts in which PARP2 is silenced by shRNA. The cytosolic electron-dense bodies resemble autophagic vesicles and, in line with that, we observed an increased number of LC3-positive and Lysotracker-stained vesicles. Silencing of PARP2 did not influence the maximal number of LC3-positive vesicles seen upon chloroquine treatment or serum starvation, suggesting that the absence of PARP2 inhibits autophagic breakdown. Silencing of PARP2 inhibited the activity of AMP-activated kinase (AMPK) and the mammalian target of rapamycin complex 2 (mTORC2). Treatment of PARP2-silenced C2C12 cells with AICAR, an AMPK activator, nicotinamide-riboside (an NAD+ precursor), or EX-527 (a SIRT1 inhibitor) decreased the number of LC3-positive vesicles cells to similar levels as in control (scPARP2) cells, suggesting that these pathways inhibit autophagic flux upon PARP2 silencing. We observed a similar increase in the number of LC3 vesicles in primary PARP2 knockout murine embryonic fibroblasts. We provided evidence that the enzymatic activity of PARP2 is important in regulating autophagy. Finally, we showed that the silencing of PARP2 induces myoblast differentiation. Taken together, PARP2 is a positive regulator of autophagic breakdown in mammalian transformed cells and its absence blocks the progression of autophagy.


    Laura Jankó, Zsanett Sári, Tünde Kovács, Gréta Kis, Magdolna Szántó, Miklós Antal, Gábor Juhász, Péter Bai. Silencing of PARP2 Blocks Autophagic Degradation. Cells. 2020 Feb 07;9(2)

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 32046043

    View Full Text