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Transcriptional targets of Drosophila JAK/STAT pathway signalling as effectors of haematopoietic tumour formation
Author(s) -
Bina Samira,
Wright Victoria M,
Fisher Katherine H,
Milo Marta,
Zeidler Martin P
Publication year - 2010
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.1
Subject(s) - biology , jak stat signaling pathway , janus kinase , effector , haematopoiesis , stat protein , signal transduction , stat , microbiology and biotechnology , janus kinase 2 , stat5 , pim1 , stat3 , cancer research , stem cell , phosphorylation , serine , tyrosine kinase
Although many signal transduction pathways have been implicated in the development of human disease, the identification of pathway targets and the biological processes that mediate disease progression remains challenging. One such disease‐related pathway is the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) cascade whose constitutive misactivation by the JAK2 V617F mutation underlies most human myeloproliferative disorders. Here, we use transcript profiling of Drosophila haemocyte‐like cells to identify JAK/STAT target genes, combined with an in vivo model for JAK‐induced blood cell overproliferation, to identify the main effectors required for haematopoietic tumour development. The identified human homologues of the Drosophila effectors were tested for potential V617F‐mediated transcriptional regulation in human HeLa cells and compared with small interfering RNA‐derived data, quantify their role in regulating the proliferation of cancer‐derived cell lines. Such an inter‐species approach is an effective way to identify factors with conserved functions that might be central to human disease.