Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of malignancies.
Signal Transducers and Activators of Transcription (STATs) are a family of proteins that mediate cytokine and growth factor induced signals playing a role in cell differentiation, proliferation, development, inflammation, and apoptosis. While other STATs can mediate pro-apoptotic or anti-apoptotic signals depending on the conditions of cell stimulation, STAT5 only demonstrates a pro-survival signal. The STAT5 induced cell survival promotion is due to regulation of transcription of genes that encode proteins which inhibit or trigger the cell death, such as the Bcl-2 family members or caspases. STAT5 is essential but not sufficient in the survival process. Signalling activators such as Ras and PI3-Kinase, cooperate with STAT5. Constitutive activation of STAT5 is associated with a wide variety of human malignancies, including leukaemia, breast, head and neck, and prostate cancers. Up-regulation of STAT5 target genes leads to changes of normal cellular growth and survival control mechanisms. Block of constitutive STAT5 activation could be a novel therapeutic approach to treat human malignancies.
Debierre-Grockiego
F
F
Institute for Virology, Med. Center for Hygiene, Philipps University, D-35037 Marburg, Germany. debierre@mailer.uni-marburg.de
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000502:physiology*; D006413:Hematopoietic System / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008894:Milk Proteins; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors