A ceramide-activated protein phosphatase mediates ceramide-induced G1 arrest of Saccharomyces cerevisiae

Joseph T. Nickels, James R. Broach

Research output: Contribution to journalArticlepeer-review

177 Scopus citations


Certain mammalian growth modulators, such as tumor necrosis factor α, interleukin-1β, and γ-interferon, induce an antiproliferative response-terminal differentiation, apoptosisis, or cell cycle arrest-through a novel signal transduction pathway mediated by the lipid ceramide as a second messenger. Both a ceramide-activated protein phosphatase and a ceramide-activated protein kinase have been implicated in transmitting the signals elicited by ceramide. We have determined that ceramide addition to the yeast Saccharomyces causes a similar antiproliferative response, resulting in arrest of cells in the G1 phase of the cell cycle. We have also determined that yeast cells contain a ceramide-activated protein phosphatase composed of regulatory subunits encoded by TPD3 and CDC55 and a catalytic subunit encoded by SIT4, Because mutation of any one of these three genes renders strains resistant to ceramide inhibition, we conclude that the G1 effects of ceramide are mediated at least in part by the yeast ceramide-activated protein phosphatase. These results highlight the conservation of signaling systems in yeast and mammalian cells and provide a novel approach to dissecting this ubiquitous signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)382-394
Number of pages13
JournalGenes and Development
Issue number4
StatePublished - Feb 15 1996

All Science Journal Classification (ASJC) codes

  • Medicine(all)


Dive into the research topics of 'A ceramide-activated protein phosphatase mediates ceramide-induced G1 arrest of Saccharomyces cerevisiae'. Together they form a unique fingerprint.

Cite this