Linked Life Data

15514480

Source:http://linkedlifedata.com/resource/pubmed/id/15514480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-10-29
pubmed:abstractText
The metabolism of glycosphingolipids is strictly regulated during the mitotic cell cycle. Before the G1-to-S transition, the ceramide and glucosylceramide concentration is elevated. Ceramide induces apoptosis synergistically with the pro-apoptotic protein prostate apoptosis response 4 (PAR-4) that may be asymmetrically inherited during cell division. Only one daughter cell dies shortly after mitosis, a mechanism we suggested to regulate the number of neural stem cells during embryonic development. The progeny cells, however, may protect themselves by converting ceramide to glucosylceramide and other glycosphingolipids. In particular, complex gangliosides have been found to sustain cell survival and differentiation. The cell cycle may thus be a turning point for (glyco)sphingolipid metabolism and explain rapid changes of the sphingolipid composition in cells that undergo mitotic cell-fate decisions. In the proposed model termed "Shiva cycle", progression through the cell cycle, differentiation, or apoptosis may rely on a delicate balance of (glyco)sphingolipid second messengers that modulate the retinoblastoma-dependent G1-to-S transition or caspase-dependent G1-to-apoptosis program. Ceramide-induced cell cycle delay at G0/G1 is either followed by ceramide-induced apoptosis or by conversion of ceramide to glucosylceramide, a proposed key regulatory rheostat that rescues cells from re-entry into a life/death decision at G1-to-S. We propose a mechanistic model for sphingolpid-induced protein scaffolds ("slip") that regulate cell-fate decisions and will discuss the biological consequences and pharmacological potential of manipulating the (glyco)sphingolipid-dependent cell fate program in cancer and stem cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0282-0080
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
315-27
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Integration of glycosphingolipid metabolism and cell-fate decisions in cancer and stem cells: review and hypothesis.
pubmed:affiliation
Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, 1120 15th Street Room CB-2803, Augusta, GA 30912, USA. ebieberich@mail.mcg.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review