Crossing paths: interactions between the cell death machinery and growth factor survival signals.
Cytokines and growth factors play a crucial role in the maintenance of haematopoietic homeostasis. They transduce signals that regulate the competing commitments of haematopoietic stem cells, quiescence or proliferation, retention of stem cell pluripotency or differentiation, and survival or demise. When the balance between these commitments and the requirements of the organisms is disturbed, particularly when it favours survival and proliferation, cancer may result. Cell death provoked by loss of growth factor signalling is regulated by the Bcl-2 family of apoptosis regulators, and thus survival messages transduced by growth factors must regulate the activity of these proteins. Many aspects of direct interactions between cytokine signalling and regulation of apoptosis remain elusive. In this review, we explore the mechanisms by which cytokines, in particular Interleukin-3 and granulocyte-macrophage colony-stimulating factor, promote cell survival and suppress apoptosis as models of how cytokine signalling and apoptotic pathways intersect.
Children's Cancer Centre, Murdoch Children's Research Institute, Royal Children's Hospital, Department of Paediatrics, University of Melbourne, Flemington Rd Parkville, Melbourne, 3052, Australia. gabriela.brumatti@mcri.edu.au
Gabriela
G
Brumatti
Marika
M
Salmanidis
Paul G
PG
Ekert
D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
D036341:Intercellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2