Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells Journal Article


Authors: Mesicek, J.; Lee, H.; Feldman, T.; Jiang, X.; Skobeleva, A.; Berdyshev, E. V.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R.
Article Title: Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells
Abstract: The role of ceramide neo-genesis in cellular stress response signaling is gaining increasing attention with recent progress in elucidating the novel roles and biochemical properties of the ceramide synthase (CerS) enzymes. Selective tissue and subcellular distribution of the six mammalian CerS isoforms, combined with distinct fatty acyl chain length substrate preferences, implicate differential functions of specific ceramide species in cellular signaling. We report here that ionizing radiation (IR) induces de novo synthesis of ceramide to influence HeLa cell apoptosis by specifically activating CerS isoforms 2, 5, and 6 that generate opposing anti- and pro-apoptotic ceramides in mitochondrial membranes. Overexpression of CerS2 resulted in partial protection from IR-induced apoptosis whereas overexpression of CerS5 increased apoptosis in HeLa cells. Knockdown studies determined that CerS2 is responsible for all observable IR-induced C24:0 CerS activity, and while CerS5 and CerS6 each confer ~50% of the C16:0 CerS baseline synthetic activity, both are required for IR-induced activity. Additionally, co-immunoprecipitation studies suggest that CerS2, 5, and 6 might exist as heterocomplexes in HeLa cells, providing further insight into the regulation of CerS proteins. These data add to the growing body of evidence demonstrating interplay among the CerS proteins in a stress stimulus-, cell type- and subcellular compartment-specific manner. © 2010 Elsevier Inc.
Keywords: signal transduction; controlled study; protein expression; unclassified drug; human cell; mammalia; apoptosis; enzyme activity; enzyme substrate; hela cell; cell type; tissue distribution; nucleotide sequence; immunoprecipitation; ionizing radiation; cellular distribution; mitochondrial membrane; cell protection; lipogenesis; cell stress; ceramide; enzyme; ceramide synthase; isoenzyme; cers; lass; ceramide synthase 2; ceramide synthase 5; ceramide synthase 6
Journal Title: Cellular Signalling
Volume: 22
Issue: 9
ISSN: 0898-6568
Publisher: Elsevier Inc.  
Date Published: 2010-09-01
Start Page: 1300
End Page: 1307
Language: English
DOI: 10.1016/j.cellsig.2010.04.006
PROVIDER: scopus
PUBMED: 20406683
PMCID: PMC4348005
DOI/URL:
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: CESIE" - "Source: Scopus"
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MSK Authors
  1. Zvi Fuks
    293 Fuks
  2. Richard N Kolesnick
    230 Kolesnick
  3. Xuejun Jiang
    79 Jiang
  4. Hyunmi Lee
    9 Lee